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Monkeypox: epidemiology, pathogenesis, treatment and prevention

Yong Huang, Li Mu, Wei Wang

Signal Transduction and Targeted Therapy · 2022 · Review · CC BY

doi:10.1038/s41392-022-01215-4

Abstract

Monkeypox is a zoonotic disease that was once endemic in west and central Africa caused by monkeypox virus. However, cases recently have been confirmed in many nonendemic countries outside of Africa. WHO declared the ongoing monkeypox outbreak to be a public health emergency of international concern on July 23, 2022, in the context of the COVID-19 pandemic. The rapidly increasing number of confirmed cases could pose a threat to the international community. Here, we review the epidemiology of monkeypox, monkeypox virus reservoirs, novel transmission patterns, mutations and mechanisms of viral infection, clinical characteristics, laboratory diagnosis and treatment measures. In addition, strategies for the prevention, such as vaccination of smallpox vaccine, is also included. Current epidemiological data indicate that high frequency of human-to-human transmission could lead to further outbreaks, especially among men who have sex with men. The development of antiviral drugs and vaccines against monkeypox virus is urgently needed, despite some therapeutic effects of currently used drugs in the clinic. We provide useful information to improve the understanding of monkeypox virus and give guidance for the government and relative agency to prevent and control the further spread of monkeypox virus.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 20, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

Monkeypox, an endemic disease in both West and Central Africa, before 2022 outbreak, a few cases were reported outside of Africa and these were associated with imports from endemic countries.– However, following the initial case diagnosed in the United Kingdom, the number of monkeypox infection have dramatically increased.,,– We are now facing the first multiple countries outbreak most with no clear epidemiological links to the endemic countries., World Health Organization (WHO) Director-General has announced the ongoing monkeypox outbreak a Public Health Emergency of International Concern (PHEIC)., The US Centers for Disease Control and Prevention (CDC) reported that as of 13 September 2022 more than 57,995 confirmed cases had been documented in 100 countries/territories (Fig. 1 and Table 1).

Monkeypox virus belongs to the Poxviridae family’s Orthopoxvirus (OPV) genus, along with variola virus (VARV, also known as smallpox), vaccinia virus (VACV), camelpox virus (CMPV), and cowpox virus (CPXV),– all of which are pathogenic for humans. There was 96.3% identity between the monkeypox virus genome’s central region, which encodes essential enzymes and structural proteins, and VARVs, which means they are highly genetically similar., In 1980, the WHO certified that smallpox had been eradicated worldwide after successful vaccination.–

Monkeypox virus has double-stranded DNA (dsDNA) as its genetic material that resembles brick-like particles ranging in size from 200–250 nm in diameter and thus can be seen by electron microscopy (magnified approximately ×10,000)., In monkeypox virus, there are two genetic clades: West Africa (WA, Clade II) clade and Congo Basin (CB, Clade I) clade,, the latter is also known as the Central African (CA) clade and more severe after infection.– In 1958, monkeypox virus was first discovered in Copenhagen among laboratory monkeys, and its first monkeypox virus infection of a human occurred in 1970 in the Democratic Republic of Congo (DRC) in a 9-month-old child, with suspected smallpox.– Monkeypox is endemic in both West Africa and Central Africa since 1970, with a mortality rate between 1 and 10%., Sequencing analysis of the current outbreak of monkeypox indicates that the virus is Western African in origin.–

Recently, the number of patients of monkeypox has increased dramatically, provoking great concern.– For this epidemic to be controlled, monkeypox virus must be better understood and re-evaluated., Here, we review the recent investigations on monkeypox, including epidemiology of monkeypox, monkeypox virus reservoirs, novel transmission patterns, mutations and mechanisms of viral infection, clinical characteristics, laboratory diagnosis and treatment measures, as well as prevention of monkeypox infection.

Epidemiology of monkeypox

It was in 1970 that the first patient of human monkeypox was diagnosed in the DRC. After that, more than 400 monkeypox patients were documented in Africa between 1970 and 1990. Of these, the vast majority were diagnosed at DRC,,– followed by 6 cases in Central African Republic (CAR), 2 cases in Cameroon,, 3 cases in Nigeria,,, 2 cases in Ivory Coast, 4 cases in Liberia, and 1 case each in Sierra Leone and Gabon. In 1990, there have been four cases of suspected monkeypox in Cameroon, one of which has been confirmed., In 1996, the DRC experienced a prolonged outbreak of human monkeypox. Initially, a patient was confirmed in February 1996, and until August of that year, a total of 71 suspected monkeypox cases were reported. As of 1999, over 500 patients of monkeypox were reported in the DRC.,– From February to August 2001, a total of 16 cases of monkeypox were identified in the province of Equateur in the DRC. Meanwhile, a study conducted by Anne et al. in the DRC from 2001 to 2004 examined vesicle fluids and crusted scabs from 136 people suspected of having monkeypox. They found 51 patients of monkeypox.

Human monkeypox attracted little attention worldwide until the first outbreak outside Africa occurred in the United States in 2003., Forty-seven cases, with confirmed (37 patients) and suspected (10 patients) monkeypox were reported, and all people infected by contact with pet prairie dogs (Cynomys spp.). The pets were infected after being in close proximity to imported small mammals (African rodents, rope squirrels (Funiscuirus spp.), tree squirrels (Heliosciurus spp.), Gambian giant rats (Cricetomys spp.), brushtail porcupines (Atherurus spp.), dormice (Graphiurus spp.), and striped mice (Hybomys spp.) from Ghana. According to CDC, laboratory tests using virus isolation and PCR amplification have proved that at least three dormice, two rope squirrels, and one Gambian giant rat were found to be infected by monkeypox. It was noted that no deaths occurred and no human-to-human transmission was observed, which was explained by the strain being a West African strain, based on genetic analysis. In addition, a study has conducted to evaluate the effects of the route of infection on the clinical illness of human monkeypox and demonstrated that significant symptoms of systemic diseases were more likely to occur in cases exposed to complex exposures than in cases exposed to noninvasive exposures (49.1 vs. 16.7%; P = 0.041). In contrast to Africa, a large number of cases confirmed in this outbreak are adults. In 2003, the Republic of Congo (ROC) reported the first outbreak of human monkeypox. It was recorded in this outbreak that 11 patients of monkeypox were confirmed and probable, all of whom were younger than 18 years of age, one death occurred. It is believed that the monkeypox virus has been transmitted from human to human six consecutive times, making it the longest recorded series of consecutive transmissions of monkeypox from one individual to another. In Unity State, Sudan, between September and December 2005, ten confirmed and nine possible patients of monkeypox were described in 5 villages (2 in Bentiu, 3 in Modin, 5 in Nuria, 5 in Rubkona, and 4 in Wang Kay). Between 2010 and 2018, varying numbers of monkeypox patients were documented in several African countries, including DRC,, CAR,– Cameroon,, Liberia, Sierra Leone, as well as COA. In addition, it was reported in 2017 that Nigeria was experiencing an outbreak. 122 confirmed or possible patients of human monkeypox were reported between September 2017 and September 2018 in 17 states in Nigeria. Six deaths were recorded (case fatality rate 6%).–

Thousands of people around the world have been infected by the monkeypox outbreak in 2022, which followed several years of sporadic cases outside of Africa (United Kingdom,– Singapore,, Israel,, United States). On May 2022, multiple cases of monkeypox were identified in the United Kingdom. On 6 May 2022, an individual with travel ties to Nigeria was diagnosed with monkeypox. On 12 May, the UK Health Security Agency (UKHSA) in London confirmed two additional cases of monkeypox. There is no link between the two of them and they have never traveled to the endemic region. A week later, another four cases were confirmed. Unusually, there was no known contact between these patients and the previous confirmed cases. By polymerase chain reaction (PCR) experiment of patient swab samples, the outbreak was caused by the West African clade of monkeypox virus, which is less fatal than the other known monkeypox variant (CB, Clade I) after infection, with a case lethally rate of only 1%.,,,

Portugal, Canada, and Spain documented 14, 13, and 7 cases of monkeypox, respectively, on 18 May.– It was also the same day that the United States identified its first monkeypox patient of 2022. On 19 May, Belgium and Sweden reported their first cases., Belgium announced that monkeypox cases were required to be isolated for 21 days at once. Belgium also became the first country in the world to require self-isolation of monkeypox cases. At the same time, Italy has reported first case, a traveler from the Canary Islands. Besides, France has reported a suspected case. Genomic analysis the virus isolated from a monkeypox virus infecting case in Portugal showed that the virus also belonged to the WA branch of evolution, closest to the virus carried by cases imported from Nigeria in 2018 and 2019. Two patients of monkeypox were confirmed in Australia on 20 May, both of whom had recently returned from travel to Europe. On the same day, the first cases were confirmed in Germany, as well as in the Netherlands and France.– On the next day, the first cases were confirmed in both Switzerland and Israel, and the patient documented by the Israeli Ministry of Health is also the first case of monkeypox in Asia.

After May 2022, a large number of monkeypox patients were confirmed in non-endemic countries worldwide. This unusual outbreak promoting the WHO to declare monkeypox as an “evolving threat of moderate public health concern” on June 23. Furthermore, the WHO announced that monkeypox outbreaks in many countries and regions constitute a “Public Health Emergency of International Concern” (PHEIC) on July 23, 2022., Meanwhile, monkeypox prevention and treatment guidelines have been issued in several countries around the world. As of 13 September 2022, 57,995 monkeypox virus infections which were laboratory confirmed have been reported in >100 countries or regions across all six WHO regions (Fig. 1 and Table 1). Of these, a total of 18 deaths were reported in 9 countries. In particular, a very recent news indicated that the first person of monkeypox was confirmed in Hong Kong on September 6. Epidemiological investigation revealed that this patient arrived in Hong Kong from the Philippines on September 5 at the age of 30 years. Consequently, as a result of the monkeypox emergence in Hong Kong, a preparedness and response plan has been activated by the Hong Kong Government. Also, this is the first reported person of monkeypox since the four cases were confirmed in Taiwan Province of China., Notably, the U.S. Centers for Disease Control and Prevention (CDC) declared monkeypox a public health emergency on August 4, 2022 in the United States. The monkeypox epidemic in the United States is extremely serious, as of September 6, monkeypox had since spread to every state, with a total of 20,733 cases.,

Monkeypox virus reservoirs

Monkeypox is a zoonotic disease whose natural reservoir remains unknown., Several researches have conducted to determine the reservoir or natural hosts of monkeypox virus, Khodakevich et al., Have reported that antibodies to the virus were found in 2 of 18 squirrels tested. The monkeypox virus was extracted from a diseased squirrel, Funisciurus anerythrus, which was the first report of monkeypox virus being isolated from a wild animal. Other researches have also suggested that squirrels of the genera Funisciurus and Heliosciurus are related to the natural cycle of monkeypox virus in DRC,– as well as Rodents of the genera Cricetomys, Graphiurus, elephant shrews of the genus Petrodromus. In March 2012, monkeypox virus was separated from a wild-living monkey (a sooty mangabey) by Radonic et al. Its whole-genome sequence showed that it had significant similarities with monkeypox viruses located in Western Africa. Patrono and colleagues described the frequent appearance of monkeypox virus in a wild-living chimpanzees (Pan troglodytes verus, hereafter chimpanzee) population from Taï National Park, Ivory Coast. A number of animal species, mostly rodents and non-human primates, have been confirmed to be susceptible to the virus after multiple investigations,, as listed in Table 2.

Novel transmission patterns

Monkeypox transmission from animals to human may include direct contact with diseased parts or body fluids of infected animals, scratching or biting by animals, eating meat from infected animals, and contact with contaminated objects.– Person to person transmission of monkeypox is caused by close contact with a human with monkeypox virus infection, including contact respiratory secretions from those infected individuals, skin lesions or genitals, prolonged face-to-face contact, along with their bedding and clothing– (Fig. 2). There is very limited data on monkeypox infection during pregnancy, although a study has demonstrated the existence of vertical transmission of monkeypox virus., At the General Hospital of Kole, an observational research was conducted, Mbala et al. described the fetal outcomes for one of four pregnant women. Of the four women, one delivered a healthy baby, one had fetal death and two delivered miscarriages in their first trimester. In addition, monkeypox virus was detected in semen sample by researchers. Therefore, more attention is needed cause individuals such as children and pregnant women are more susceptible with increasing cases.,,– Notably, a very recent report proved that human-to-dog transmission of monkeypox virus. Next-generation sequencing was used to compare the DNA sequences of the monkeypox virus from the dog and the patient. The samples both contained viruses of the human monkeypox virus-1 clade, lineage B.1, that have been spreading in countries that are not endemic to the disease.

According to previous reports, monkeypox virus was not previously been highly contagious. Monkeypox of the CB clade was found to have a lower basic reproduction number (R0) than 1 between 1980 and 1984 in the Democratic Republic of the Congo., Disseminated patients of monkeypox have been recorded in Africa, usually because of close contact with wild animals, especially rodents. Such travel related monkeypox individuals have limited secondary spread, making human-to-human transmission inefficient.,, However, a recent study by Du et al. reported that the reproduction number was estimated to be 1.39 (95% CrI: 1.37, 1.42) by aggregating all patients in 70 countries as of July 22 2022. According to initial estimates based on analysis of the first 255 PCR-identified patients of monkeypox in Italy in 2022, the reproduction number among men who have sex with men is 2.43 (95% CI 1.82–3.26). Which indicates that the disease has epidemic potential. Meanwhile, the vast majority of monkeypox patients had not recently traveled to the endemic regions of Africa, such as Nigeria, the DRC as well as central and western Africa. Human-to-human transmission of this virus is unusually frequent in this outbreak, suggesting close contact is the most likely route of transmission.

Another unusual feature is that the large number of cases diagnosed with monkeypox are male, and a considerable part of patients have sex with men (MSM), particularly in Canada, Spain, and the UK, suggesting that sexuality is another forms of close contact, even though monkeypox was not considered a sexually transmitted disease before.– It is reported that higher proportion of MSM infected is due to accidental entry into the community and then sexual behavior constituting “close contact” rather than sexual transmission of the monkeypox virus itself. However, a study of samples from 528 confirmed cases outside endemic areas in Africa between April and June showed that 98% of patients were bisexual men or gay and 95% of those infected were suspected of transmission through sexual activity. A prospective cohort study in Spain indicated that 91.7% cases identifying as MSM in 181 monkeypox infection cases. Besides, monkeypox virus DNA was detected by PCR in seminal fluid in 29 of the 32 cases. On 3 August, In the Monkeypox Surveillance Bulletin published by the ECDC-WHO Regional Office for Europe, 99% (15,439/15,572) of the cases were males, with 43.4% of MSM cases. Meanwhile, using a branching process transmission model, researchers showed that a small minority of people have disproportionately large numbers of partners, which could explain the continued increase in monkeypox patients among MSM population. Another research showed a transmission number of 2.43 in the MSM community among Italian cases in May-June 2022. According to Endo and colleagues, monkeypox’s basic reproductive number (R0) may be significantly higher than 1 over the MSM sexual contact network. Monkeypox virus spread model for assessing outbreak risk in a metropolitan area indicated that if transmission efficiency increases in the higher-risk group like gays and MSMs, broader populations may be affected. On the other hand, Bragezzi et al. conducted a meta-analysis to show that sexual contact is involved in 91% cases (total 124 cases). Notably, a recent study of 21,098 monkeypox cases (data from 41 countries, as of August 23, 2022) revealed that the vast majority were MSM, with a typical rash characteristic. Transmission was mainly through close contact during sexual activities. Overall, all these reports suggested that MSM was up to now the most frequently suspected route of transmission.,,– Consequently, targeted interventions are needed in communities with a large part of MSM individuals to prevent further transmission. And further research is demanded to determine whether sexual transmission is possible.

Monkeypox virus mutations and mechanisms of viral infection

Monkeypox virus is a species of double-stranded DNA virus which causes monkeypox in humans and other animals. It belongs to the genus Orthopoxvirus in the family Poxviridae. Among all animal viruses, poxviruses have the largest and most complex DNA genomes., There are four major elements of the virion: core, lateral bodies, outer membrane, and the outer lipoprotein envelope. The central core contains the viral dsDNA and core fibrils. The monkeypox virus genome consists of 197 kb with the central genomic region comprising of 101 kb. Both terminal variables regions include a 6379 bp terminal inverted repetition (ITR) with approximately 80 bp long hairpin loop, 70 or 54 bp short tandem repeats and unique ITR sequences NR 1 and NR 2 and the coding region.,, The virus contains about 190 nonoverlapping open reading frames (ORFs),,,, four of which are located in the ITR sequence. Genes responsible for viral replication, transcription, assembly, and release are conservatively located in the genome’s central region, as they are in all orthopoxviruses. While most of the genes expressing virulence and host tropism are found at both ends of the genome. These terminal genes play a role in immune evasion by interfering with signaling, presentation, and recognition of antigens and apoptosis.–

Monkeypox virus has a low frequency of genomic mutations, due to the DNA double-stranded structure, and the 3’–5’ exonuclease activity of its DNA polymerase., However, the 2022 monkeypox virus diverges from the related 2018–2019 viruses by a mean of 50 single-nucleotide polymorphisms (SNPs), considering previous estimates of the substitution rate for orthopoxviruses, this is much higher than expected., Such a divergent branch could speed up the evolution of the monkeypox virus. Notably, further examination of the mutational profiles of these SNPs suggested a dramatic mutational bias, with 26 (14 non-synonymous, 10 synonymous, and 2 intergenic) and 15 (nine non-synonymous and 16 synonymous) being GA>AA and TC>TT nucleotide replacements, respectively. Several studies have indicated that mutations observed in viral genome editing may be caused by apolipoprotein B mRNA-editing catalytic polypeptide-like 3 (APOBEC3) enzymes.– Another phylogenetic analysis indicated that the monkeypox virus‐2022 strains contained 46 new consensus mutations, including 24 nonsynonymous mutations, compared with the monkeypox virus-2018 strain. We suspected that the lower mortality and higher transmission of 2022 monkeypox virus than previous monkeypox virus may related to these viral mutations. Although these viruses are under continual adaptation, it is unknown whether these mutations contribute to help the virus evade host immunity. To further understand how these mutations affect viral function, additional research is required.

Unlike other DNA viruses, monkeypox virus replicates in the cytoplasm of the host cell. Poxviruses enter into the host cell may be divided into 3 steps (Fig. 3): virus attachment, hemifusion, and core entry, which occurs at the cell membrane or following endocytosis.,, A unique feature of poxviruses is that they produce two types of infectious particles: extracellular virions (EVs) and mature virions (MVs), both viral particles have different viral surface epitopes. Poxviruses enter cells through different mechanisms depending on their infectious forms, mature virion (MV) with single outer membrane, or enveloped virion (EV) with additional membrane and different protein composition.–

Despite not being able to identify specific receptors for poxviruses, many glycosaminoglycans including heparin sulfates and chondroitin, as well as laminin, contribute to their attachment to cells.,, Up to now, many researches have been demonstrated that several vaccinia virus proteins are vital for binding to the cell surface, including D8L,, A27L,, A34R,– A26L and H3L.– It is following viral attachment that the virion binds to the membrane and fuses with the host cell, causing its core to be released into the cell’s cytoplasm. Virion core contains enzymes and factors that initiate transcription. It was proven that L1, F9, A28, A27, L5, H2 were essential viral envelope proteins for cellular entry.– Virus-encoded multi-subunit DNA-dependent RNA polymerase initiates viral transcription, which is followed by host ribosome-mediated translation of early, intermediate, and late proteins. The intermediate and late stages of viral gene transcription require cooperation with host-derived transcription factors.– Synthesis of poxvirus DNA occurs in the cytoplasm. A majority of viral particles remain in the cytoplasm as intracellular mature virions (IMVs) and are encased within the protein matrix of scabs. A second envelope (intracellular enveloped virions, IEVs) may be acquired by the remaining virions, and they are attached to the cell membrane of their host. As cell surface-associated enveloped virions (CEVs), they cause cell-to-cell transmission of the virus, while extracellular enveloped virions (EEVs) contribute to systemic transmission.

Clinical characteristics

The clinical characteristics of monkeypox are quite similar to those of smallpox, but the monkeypox is clinically milder.,– It is crucial to realize that monkeypox and smallpox differ mainly by the occurrence of lymphadenopathy, since 90% of monkeypox patients suffer from lymph node enlargement. Monkeypox is most commonly confused with chickenpox, caused by varicella-zoster virus (VZV). In terms of their clinical characteristics, these two diseases share a great deal in common. Moreover, several studies have reported that individuals are infected both monkeypox virus and VZV.,,

The incubation time of monkeypox virus is usually 5–21 days.,,, According to Miura’s report, incubation period (18 cases) is estimated to be 8.5 days on average. Based on 22 possible (N = 1) and confirmed (N = 21) monkeypox patients reported in the United States through 6, 2022, Charniga and colleagues estimated the incubation time for monkeypox. According to their study, the incubation time from exposure to the onset of symptoms was 7.6 days on average. Besides, another research found that among 23 people with known history of exposure, the median incubation period was 7 days (between 3 and 20 days).

In humans, monkeypox disease can be divided into two phases: the prodrome and the rash. Initial symptoms of monkeypox virus infection include headache, lack of energy, fever, chills and/or sweats, sore throat, muscle ache, and lymphadenopathy,– (Fig. 2). Usually, few days after fever and lymphadenopathy, the rash appears. Rash starts with the face and then appears the whole body, and is characterized by a few to several thousand lesions.,, As the rash progresses about 2–4 weeks, plaque is replaced by papules, blisters, pustules, scabs, followed by shedding.,, Complications of monkeypox include encephalitis, keratitis, pneumonitis, and secondary bacterial infections.,,,

In the United States, a report on the epidemiological and clinical features of monkeypox cases showed 42% of persons (n = 291 participants) has no prodromal symptoms, and 37% of patients did not have fever as of the time of assessment, despite most patients included typical features. And genital rashes were observed in many cases, which was also recently proven in another studies.– Other recent reports describe similar clinical characteristics.,, Patel and colleagues demonstrated that all 197 monkeypox infection cases developed mucocutaneous lesions, typically in the genitals (111 of 197 patients) or the perianal areas, causing rectal pain and penile edema. Moreover, according to a case report from Spain, 78 of 181 persons had lesions in the oral and perioral region and 141 in the anogenital region. The following complications occurred in 70 of the 181 patients: 45 (24.9%) of 181 had a proctitis, 19 (10.5%) tonsillitis, and 6 (3.3%) had a bacterial skin abscess. The clinician should remain vigilant for monkeypox-like rashes regardless of whether the rash has disseminated or had a prodrome prior to the rash. Notably, the possibility of some monkeypox virus infections being asymptomatic has been raised by two recent case reports from Europe. It has been shown in several studies that monkeypox could go unobserved when it is propagable, so physicians and persons at high risk should be aware of this fact.,,

Available data from the European Union, the United Kingdom, and the United States indicated that 28–51% have human immunodeficiency virus (HIV) infection among MSM patients with monkeypox.,,,,, Currently, the risk for monkeypox infection is unknown, however, in people with HIV.

Symptoms of monkeypox last 2–4 weeks, and the disease is usually self-limiting. The lethality of monkeypox patients after infection depend on the clade of virus infected, route of infection, patient age, and patients infected with the CA clade of the virus is generally higher than the WA clade.,,, Previous reports,,,– indicated that the case fatality rates (CFR) of monkeypox ranging from 1 to 11%. What’s more, in a systematic review that exclusively evaluated the case fatality rates (CFR) by clades, the overall rate of case fatalities was confirmed to be 8.7%, which was significantly lower for West African clade (3.6%, 95% CI 1.7–6.8%) than Central African clade (10.6%, 8.4–13.3%)., Among 1958 patients, some 4% (95% CI 1–9%) of hospitalized patients had fatal outcomes. In the current 2022 monkeypox outbreak, it was reported that patients at least sixteen years old always have milder symptoms in the current investigations, with a pooled case fatality rate of 0.03% (1 of 2941 patients). Monkeypox is more often fatal in children, which is similar to smallpox., As of September 2022, a total of 15 deaths have been documented in this monkeypox global outbreak, in which 9 deaths in locations that have historically recorded monkeypox.

Laboratory diagnosis

Diagnosis of monkeypox requires a combination of clinical symptoms, epidemiological information, and laboratory tests. According to WHO recommendations, nucleic acid amplification testing (NAAT) has been conducted for monkeypox virus detection. Genes commonly used for conventional polymerase chain reaction (PCR) testing include hemagglutinin, the acidophilic-type inclusion body gene,, and the crmB gene. Compared with other diagnostic methods, real-time PCR provides high throughput, high sensitivity, and fast results. Several genes have been developed to detect monkeypox virus, such as envelope protein gene (B6R), B7R gene, DNA polymerase gene E9L,, complement binding protein C3L,, DNA-dependent RNA polymerase subunit 18 (RPO18) gene, F3L and N3R. Meanwhile, recombinase polymerase amplification (RPA) method has been proven to be an alternative to real-time PCR. It was reported that the monkeypox virus-RPA-method was especially sensitive with a limit of detection (LOD) of 16 DNA molecules per microliter by targeting the tumor necrosis factor binding protein gene. With different target sites in the viral genome, these tests have varying sensitivities and limits of detection for monkeypox virus. According to Li et al. real-time PCR assay for generic monkeypox virus has a limit of detection for 0.7 fg (∼3.5 genomes), while monkeypox virus West Africa specific (G2R_WA) assay’s LOD is at 1.7 fg (∼8.2 genome), and monkeypox virus Congo Basin (C3L) assay’s LOD is at 9.46 fg (∼40.4 genomes). As well, Maksyutov et al. developed real-time PCR assay that targets viral F3L gene with a LOD of 20 copies per reaction. Several other studies reported LOD for monkeypox virus assays of 6.359 copies/mL, 20 copies/reaction, 11–55 fg (50–250 copies of each gene), 2 fg (~10 viral copies), 0.05 fg (25 copies/assay).

Recently, a high-throughput molecular testing method for monkeypox virus was established, which may expand the detection capacity and reduces the detection of time. In the current outbreak, the whole genome sequencing was also used to identify the monkeypox strain.,,, What’s more, there are several other DNA-based assays have been investigated for monkeypox virus detection, such as loop-mediated isothermal amplification (LAMP), restriction length fragment polymorphism (RFLP),, as well as recombinase polymerase amplification (RPA).

Laboratory methods for detecting monkeypox also include enzyme-linked immunosorbent assay (ELISA),, western blot (WB), and immunohistochemistry (IHC)., It is often necessary to use serologic diagnostic procedures to diagnose poxvirus when there is no virological sample. In most cases, ELISA is the most frequently used serologic test. Serological testing of the specific IgM and IgG antibodies are commonly deployed. As soon as the rash appears, IgM antibodies appear and rise approximately 2 weeks before declining and disappearing within 1 year. While IgG antibodies also generate quickly after the rash onset, rise approximately 6 weeks, and lasts for decades. However, the specificity is low, due to the immunologic cross-reactivity between monkeypox virus and other othopoxviruses., Electron microscopic observation can be used as an auxiliary method to detect monkeypox virus., However, due to the laborious and costly sample preparation, it is difficult to be used popularly.

Treatment

Treatment is suggested for monkeypox virus-infected individuals with severe disease at present or who may be at high risk for developing serious illness (people who are immunocompromised, pediatric population, have characteristic dermatitis or history, have skin symptoms of exfoliation, pregnant or breastfeeding woman, one or more complications), or those with monkeypox virus aberrant infections, including accidental implantation in mouth, eyes, or other anatomical areas where monkeypox virus infection that could pose a special threat (such as the genitals or anus). For most patients, treatment is symptomatic and supportive. Despite the fact that monkeypox has no specific treatment, smallpox antiviral drugs such as brincidofovir, tecovirimat, and cidofovir may have effect against monkeypox because of their similar genetics.,–

Tecovirimat

Tecovirimat (also known as TPOXX, ST-246), a small-molecule inhibitor of virus, is effective against orthopoxviruses both in vitro and in vivo, including vaccinia virus, camelpox virus, cowpox virus, mousepox virus, variola viruses, and monkeypox virus. Tecovirimat targets the VP37 protein, inhibits the spread of viruses within the body by preventing them from leaving infected cells,, as shown in Fig. 3. Tecovirimat inhibits neither DNA or protein synthesis nor the formation of mature virus. The mature virus remains in the host cell until cell lysis. Tecovirimat displayed s strong antiviral efficacy with an EC50 range of 0.01 to 0.07 μM.,, Several studies have demonstrated that the VP37 protein plays an essential role in encapsulating intracellular mature virus with Golgi-derived membrane to form enveloped virus.,–

Tecovirimat has a distinguished antiviral effect against the monkeypox virus lineage responsible for the 2022 outbreak in vitro. Further, the effectiveness and safety of tecovirimat has been revealed in multiple animal studies.– Treatment with 10 mg per kilogram of body weight of tecovirimat for 14 days in the monkeypox model could achieve >90% survival. In a nonhuman primate (NHP) model, by taking orally once a day, tecovirimat was found to be effective in protecting NHP from monkeypox virus illness, with reduced viral loads, fewer rashes, prolonged survival and significantly reduced mortality in the treatment group compared with the vehicle mongkeys. Smith et al. assessed the efficacy of tecovirimat against monkeypox virus challenge of 65 times the 50% lethal dose (LD50) in prairie dogs, and found that one hundred percent of animals that received tecovirimat survived challenge, while 75% of infected animals receiving vehicle alone succumbed to infection. Meanwhile, multiple phase 3 clinical trials of tecovirimat have demonstrated its safety and well tolerated (Table 3).

In 2018, the FDA approved its first use for treating smallpox after studies showed it was safe in humans and effective in animals with similar viruses.,,, A trial in monkeypox people showed the tecovirimat (600 mg twice daily for 2 weeks orally) did not cause side effects and that viral shedding and illness lasted shorter time. Besides, data collected from 25 cases with diagnosed monkeypox infection had completed a course of tecovirimat therapy revealed all cases tolerated the antiviral medicine well, with minor side effects. The lesions and pain of 10 patients (40%) were completely resolved by day 7 of therapy, and 23 of 25 patients on day 21. The most frequently adverse events of therapy reported including diarrhea in 2 (8%), itching in 2 (8%), nausea in 4 (16%), headache in 5 (20%), and fatigue in 7 patients (28%). Moreover, several reports have also documented the efficacy and safety of tecovirimat in the treatment of monkeypox.,– Healthcare providers can now provide tecovirimat treatment to monkeypox patients under an expanded access Investigational New Drug (EA-IND) protocol developed by CDC and FDA. A total of 1001 cases receiving this antiviral drug have been documented, in addition, data was abstracted by the Centers for Disease Control.

Despite this, more clinical trials are needed to determine whether this antiviral drug is effective and safe for treating monkeypox infections in people. A double-blind, randomized controlled study will be conducted by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Disease (NIAID) in treating individuals confirmed with monkeypox in adults and children to evaluate the effectiveness and safety of tecovirimat. Meanwhile, through the AIDS Clinical Trials Group, NIH/NIAID is conducting a phase 3 double-blind, randomized controlled investigation of tecovirimat in outpatient in the United States settings to treat monkeypox. According to the latest report, it is currently underway or planned to conduct several clinical experiments to evaluate tecovirimat’s safety and effectiveness in treating monkeypox patients (PALM-007, PLATINUM, WHO/ARNS, and ACTG5418).,

Cidofovir

Since 1996, Cidofovir (CDV, also known as Vistide) has been approved for clinical use to treat cytomegalovirus (CMV) retinitis in persons with acquired immunodeficiency syndrome (AIDS).– CDV is a prodrug, and it must be phosphorylated by enzymes of the cytoplasm after enter the host cells, and into CDV diphosphate (CDV-pp), which has a prolonged half-life.– CDV-pp inhibits the viral DNA polymerase during DNA replication, as well as inhibits DNA polymerase 3′–5′ exonuclease activity.

Many animal models and experiments in vitro have reported the effectiveness of cidofovir for treatment orthopoxviruses, including vaccinia, mousepox, as well as monkeypox.,– Between 72 to 96 h post-infection, treatment of mice inoculated with cowpox virus (CV) or vaccinia virus (VV) resulted in significant protection. And when given at least 5 days before infection or 3 days after infection with either VV or CV, a single-dose pretreatment or posttreatment with CDV at 3 to 100 mg/kg was effective. Another mouse model demonstrated that it was completely protective against virus-induced cutaneous lesions and against the associated mortality when started on the day of infection or the first post-infection day of topical treatment with cidofovir. In addition, systemic treatment with cidofovir caused lesions to heal and regress. The treatment of mice with cidofovir (for two days after 24 h of virus exposure) suppressed viral loads as well as cytokine levels in plasma and tissue, including interleukin (IL)-10, IL-6, IL-3, and IL-2. In non-human primate model, researches proved a significant reduction in mortality and cutaneous monkeypox lesions when CDV treatment is initiated 24 h after lethal intratracheal monkeypox virus infection.

Various studies have shown the effectiveness of CDV against poxvirus. Patients with recalcitrant molluscum contagiosum virus (MCV) treated with intravenous cidofovir exhibited dramatic cleaning of their MCV lesions, and all three cases remain clean of recurrence. The use of topical CDV was found to be effective in treating molluscum contagiosum (MC) in a 12-year-old boy with Wiskott–Aldrich syndrome. Two children with AIDS were also successfully treated with topical 3% cidofovir in a combination vehicle (Dermovan) for recalcitrant MC. CDV has also been documented to be effective against cowpox and human vaccinia in additional case reports.– Despite the lack of clinical evidence to support its use in treating monkeypox, cidofovir is generally thought to be effective. According to the CDC’s guidance, an outbreak of orthopoxviruses, including monkeypox virus, can be treated with this anti-viral medicine.

Brincidofovir

Brincidofovir (also known as CMX001 or Tembexa) is a lipid conjugate of the acyclic nucleotide phosphonate, cidofovir (CDV). After brincidofovir entry into target cells, a phospholipase enzyme cleaves the lipid ester linkage in brincidofovir, liberating CDV and activated by two sequential phosphorylations, first yield cidofovir monophosphate (CDV-P) and then yield cidofovir diphosphate (CDV-PP). CDV-pp suppresses the synthesis of viral DNA by inhibiting the DNA polymerase activity of several double-stranded DNA (dsDNA) viruses or by acting as an acyclic nucleotide and binding to the viral DNA strand– (Fig. 3).

Brincidofovir has under gone numerous animal studies,– to demonstrate its antiviral efficacy against double-stranded DNA viruses including poxviruses such as monkeypox virus and is currently in human clinical investigations for treating other double-stranded DNA viruses (Table 3). In addition, An antiviral regimen with brincidofovir and ST-246 administered on the day of monkeypox virus infection protects mice with the STAT1-deficient C57BL/6 mouse model. Lethal rabbitpox models revealed that brincidofovir administration at or before the midpoint of illness could reduce the fatality rate from rabbitpox virus infection, as well as reduce viral loads, which might contribute to decrease infectivity of the virus., Studies have been conducted using the prairie dog monkeypox virus model to determine the effectiveness of anti-poxvirus therapeutics., In a monkeypox virus animal model, brincidofovir was administered orally to prairie dogs to determine its pharmacokinetics (PK). It was found that BCV treatment early in the illness tended to increase survival against a lethal monkeypox virus challenge; the earlier the treatment was initiated, the greater the chance of survival., In summary, these models suggest that treating monkeypox patients early with brincidofovir is more likely to have better outcomes.

In 2021, Brincidofovir was licensed by the FDA for treating human smallpox disease in both adults and children. To facilitate the use of brincidofovir for the treatment of monkeypox, the CDC is currently developing an Expanded Access Investigational New Drug. In comparison with cidofovir, brincidofovir has higher intracellular levels of the active drug, well oral bioavailability, superior antiadenoviral activity, and no nephrotoxicity.,,– The complete resolution in a patient with progressive vaccinia (PV) demonstrated the effectiveness of brincidofovir in combination with other antiviral drugs. Recent research, however, indicates brincidofovir is associated with serious adverse effects in monkeypox patients. Over the past three years, three cases have experienced liver toxicity in the United Kingdom. Further studies are warranted in humans regarding the efficacy of brincidofovir against monkeypox virus.

VIGIV

Vaccinia immune globulin intravenous (VIGIV), a FDA-approved medicine, is applied to treat smallpox vaccination complications such as severe generalized vaccinia, vaccinia infections in people who have skin conditions, eczema vaccinatum, progressive vaccinia and aberrant infections induced by vaccinia virus (excluding isolated keratitis). Vaccinia immune globulin (VIG) is a sterile solution made up of high titers of IgG antibodies against the vaccinia virus taken from healthy persons who had been previously vaccinated against the live vaccinia virus. CDC allows the use of VIG for the treatment of monkeypox in an outbreak. Several studies have reported the patients received VIGIV for the treatment of orthopoxvirus infection.– Nevertheless, data on VIG’s effectiveness in treating monkeypox virus infection are unavailable. Physicians may consider using it in severe cases. The VIG is also suitable for prophylactic use in persons with severe immunodeficiency in T cell function for whom smallpox vaccination is contraindicated after exposure to monkeypox virus.

Monkeypox prevention

To prevent getting monkeypox, CDC suggest that people need to avoid close, skin-to-skin contact with someone who has monkeypox-like rashes, avoid contact with objects and materials that a case with monkeypox has used, use hand sanitizers that contain alcohol before eating, touching the face, and wash your hands frequently after using the bathroom.

There is no vaccine specifically designed to prevent monkeypox virus infection. Owning to immunological cross protection among orthopoxviruses,,,– smallpox vaccines (vaccinia virus-based) were recommended for use in the current outbreak of monkeypox.,– Epidemiological data on human monkeypox collected in Zaire from 1980 to 1984 revealed that there was a significant difference in attack rates between contacts without a vaccination scar and those who had been vaccinated in the past (7.2% vs. 0.9%). Rimoin et al. suggested that monkeypox incidence increased dramatically in the DRC 30 years after smallpox vaccination campaigns ended. Furthermore, their data suggested that vaccine-induced immunity lasts a long time as individuals vaccinated against smallpox >25 years ago are still at reduced risk of monkeypox today. As demonstrated by the US monkeypox outbreak of 2003, smallpox vaccination can potentially sustain cross-immune protection against West African monkeypox for decades afterward. Three individuals who had not previously been infected with monkeypox virus and had been vaccinated against smallpox for decades were unaware of their subsequent infection because none of them had any clinical characteristics associated with the monkeypox.

Studies have reported that first-generation live vaccinia vaccines can provide approximately 85% protection against monkeypox infection due to cross-reactive antibodies that can be induced by orthopoxviruses. Second-generation vaccine is ACAM2000, a live attenuated vaccinia vaccine approved in the USA in August 2007 for prevention of smallpox, (Fig. 4). Its effectiveness has been demonstrated in both animal models,– and clinical trials (Table 3).

Assessment of the protective effect against aerosolized monkeypox virus in cynomolgus macaques revealed that a single immunization with ACAM2000 vaccines were protected completely. Monkeys challenged with lethal monkeypox virus after vaccinated with the ACAM200 live attenuated smallpox vaccine, all (N = 12) vaccinated treated monkeys survived. In a prairie dog model, for ACAM2000, the vaccine administered at 1 day postexposure was similarly effective with the vaccine administered at 3 days postexposure, resulting in 50–62% survival, compared with only 25% survival in the unvaccinated group. Taken together, ACAM2000 is likely effective at preventing monkeypox; however, due to its potential for replication, it may cause severe side effects, including progressive vaccinia, eczema vaccinatum, and myopericarditis.,,– A person with a weak immune system, including someone with HIV, pregnant women, and those who suffer from skin conditions like eczema, are not advised to use it.,

The third-generation vaccine, modified vaccinia Ankara (MVA, JYNNEOS in the United States, IMVANEX in the European Union, and IMAMUNE in Canada), was approved in individuals 18 years of age or older considered to be more susceptible for smallpox or monkeypox infection in US to prevent both smallpox and monkeypox disease in 2019. Unlike ACAM2000, JYNNEOS is a nonreplicating vaccine, which will not lead to the production of live virus. As a smallpox vaccine, JYNNEOS has demonstrated good immunogenicity, safety, and efficacy both in animal models and clinicals.– It was the only currently FDA-approved vaccinia vaccine for the prevention of monkeypox disease (Fig. 4). Several animal model studies exhibited good protective effects against monkeypox,,– furthermore, in macaque challenge trials 100% protection against monkeypox infection was demonstrated, along with long lasting immunity, and long lasting protective immunity for a lethal monkeypox challenge. Petersen et al. evaluated its effectiveness, immunogenicity, and safety in healthcare workers at risk of monkeypox virus infection in the DRC. Meanwhile, another human clinical investigation examining the effectiveness of monkeypox vaccination after exposure is currently underway. Numerous clinical trials of MVA have proved the efficacy and safety of JYNNEOS, as listed in Table 3.

As a result of the outbreak of monkeypox in 2022, several countries, including the United States, Spain, Germany and the United Kingdom, have announced they are buying vaccines and/or releasing vaccines them from national stockpiles to combat the epidemic. JYNNEOS is being used by the US for pre-exposure vaccination of people who are at risk of occupational exposure to orthopoxviruses according to CDC announcements made in May 2022., Meanwhile, in its interim guidance for monkeypox vaccines, WHO recommended post-exposure prophylaxis (PEP) ideally within 4 days of the first exposure, pre-exposure prophylaxis (PrEP) is recommended for health workers at risk, clinical laboratory staff performing diagnostic testing, laboratory personnel working with orthopoxviruses, and others at risk under national policy. IMAMUNE is approved for immunization against monkeypox and Orthopox virus by the Public Health Agency of Canada (PHAC), and IMVANEX is recommended by the European Medicine Agency (EMA) for monkeypox prevention., By July 27, 786,000 more doses are expected to be released that week after the federal government distributed 300,000 doses of vaccine to state and local health authorities and clinics throughout the country. JYNNEOS is manufactured exclusively by Bavarian Nordic, which has a limited production capacity. Recently, due to the vaccine shortage, Bavarian Nordic has expanded its capacity by working with U.S. contract manufacturer to fill smallpox/monkeypox vaccines. In addition, a European Union Authorization (EUA) was approved by the FDA for the JYNNEOS vaccine, allowing healthcare providers to administer it intradermally to individuals 18 years of age and older who have been considered to be more susceptible for monkeypox infection. Individuals vaccinated intradermally were less vaccinated (by one-fifth) than those vaccinated subcutaneously (SC). The total dose available for use could increase by five-fold as a result. A study with lower intradermal doses of MVA was found to be immunologically noninferior to the standard subcutaneous dose (NCT00914732).

In 1975, the other smallpox vaccine, LC16m8, was licensed for active immunization against smallpox in Japan. This vaccine is derived from the Lister (Elstree) strain of vaccinia and is a live, replicating, attenuated 3rd generation vaccine. This high attenuation resulted from a single nucleotide deletion mutation in the B5R viral gene, resulting in a truncated membrane protein B5, which is one of the most immunogenic proteins.– Several animal model challenge studies of safety and efficacy of LC16m8 have been conducted in mouse,,– rabbit,, and nonhuman primates., Both the intranasal and subcutaneous inoculation models showed no symptoms of monkeypox after immunization with LC16m8. A single vaccination of non-human primate model revealed that LC16m8 exhibited long-lasting protection against monkeypox virus, evidence from the reduction in viremia and the IgG antibody response. Notably, another nonhuman primate model revealed that for immunocompromised individuals, LC16m8 is a safer and more effective alternative to ACAM2000 and Dryvax (first-generation vaccines). LC16m8 was shown to produce neutralizing antibodies for vaccinia, monkeypox, and variola major, as well as broad T cell responses in a phase I/II clinical trial. In addition, various immunogenic studies in human have confirmed a good safety profile about LC16m8.– In summary, these results reveal that LC16m8 may be effective for preventing people against monkeypox. Japanese authorities expanded the range of indications for this vaccine to include protection against monkeypox in August 2022.

Conclusion and perspectives

Monkeypox, COVID-19, and polio are among the three emergencies that WHO has declared worldwide at the moment. Monkeypox is now an international problem after previously being endemic to Africa. Until September 2022, more than 56000 patients have been diagnosed in the monkeypox 2022 outbreak. Monkeypox infection patients are rapidly increasing around the world, it is likely to be caused by a combination of natural and human factors. On the other hand, there has been an increase in human–wildlife contact due to climate change, deforestation, and the Ukrainian–Russian war, among other factors. In addition, it is still possible that monkeypox virus will become more prevalent due to the cessation of smallpox vaccination with vaccinia vaccine in 1980. Currently, in spite of the fact that mass vaccination is not recommended or achievable, individuals manage monkeypox may though vaccine (post-exposure prophylaxis, or pre-exposure prophylaxis), anti-viral medicines, as well as isolate or quarantine of the patients and any contacts with the patients.

Particularly, there are large number of patients have been confirmed in MSM population in this 2022 outbreak and has been related to unanticipated anal and genital lesions, suggesting the monkeypox virus may be spreading via sexual transmission.,,,,, This novel transmission pattern was suspected during 2017 outbreak of human monkeypox in Nigeria, but was not proven. Meanwhile, MSM population has higher risk on other disease through sexual transmission, such as HIV. In Ogoina and colleagues’ study, it was reported that monkeypox patients in Nigeria who were HIV-positive had longer-lasting illness, and larger lesions, and a higher percentage of and genital ulcers and secondary bacterial skin infections. By contrast, Tarin-Vicente and his colleagues reported that there was no difference between HIV-positive patients and the rest of the population in terms of severity or progression of the disease. Therefore, more investigations are needed to understand the effectiveness of anti-viral treatment among individuals infected with both HIV and human monkeypox virus. Besides, in order to reduce monkeypox transmission within MSM groups, public health efforts must deal with challenges including homophobia, stigma, and discrimination.

Given the current global monkeypox epidemic, a race to create monkeypox -specific vaccines may occur like COVID-19 (Fig. 4). Moderna has announced that they have initiated a program to consider whether developing an mRNA monkeypox vaccine or not because of growing demand for vaccination, even though no further information on the vaccine or potential development timeline was released latter. Meanwhile, the U.S. Patent and Trademark Office (USPTO) has addressed a patent to the Tonix Pharmaceuticals company for its vaccine candidate namely TNX-801, which was designed to protect against smallpox and monkeypox. TNX-801 is a novel, horsepox-based live virus vaccine based on synthesized horsepox (sHPXV). Effectiveness and safety have been demonstrated both in mouse models previously. In addition, TNX-801 vaccination protects macaques from monkeypox challenge, no lesions were seen in all monkeys. The monkeypox virion membrane surface-binding protein E8L is vital for virus attachment to host cells, which may be also used to explore new vaccine against monkeypox. Importantly, knowledge of the immunological response and mechanism of monkeypox virus infection would be critical, providing new ideas for vaccine development. Identification of the genes responsible for the host-range defect of virus may engineer more effective and safe vaccines, such as C16L/B22R, C16L (MVA genome). For severely immunocompromised individuals, valid vaccination strategies that bypass CD4 negative cell help are needed to protect against virus.

Global public health has been severely tested by the COVID-19 pandemic in the past two years. Confirmed cases of monkeypox are increasing rapidly worldwide especially in the US, which may have a negative impact on the global economy. With monkeypox being announced a public health emergency of international concern by WHO, people should raise awareness and build diagnostic capacity for the monkeypox epidemic in order to limit further spread of the virus. We should improve understanding and clinical management of monkeypox, as well as infection prevention and control skills, especially among public health personnel. At the same time, stigma and discrimination within the MSM community should be properly addressed and equitable access to treatment and vaccines should be ensured. Finally, we should initiate a global collaboration to conduct clinical investigations to test the efficacy and safety of monkeypox vaccines as well as antiviral drugs.

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    Vaughan, A. M. et al. A large multi-country outbreak of monkeypox across 41 countries in the WHO European Region, 7 March to 23 August 2022. Euro Surveill. 27, 2200620 (2022).

    Not in our library10.2807/1560-7917.es.2022.27.36.2200620

  187. 187.

    Graham, F. Daily briefing: how monkeypox might be spreading in sexual networks. Nature10.1038/d41586-022-01726-8 (2022).

    Not in our library10.1038/d41586-022-01726-8

  188. 188.

    Zhu F, Li L, Che D. Monkeypox virus under COVID-19: caution for sexual transmission - correspondence. Int J. Surg. 2022;104:106768.

    Not in our library10.1016/j.ijsu.2022.106768

  189. 189.

    Rodriguez-Morales, A. J. & Lopardo, G. Monkeypox: another sexually transmitted infection? Pathogens. 11, 713 (2022).

    Not in our library10.3390/pathogens11070713

  190. 190.

    Brockmeyer NH. As monkeypox goes sexual: a public health perspective. J. Eur. Acad. Dermatol. Venereol. 2022;36:1164-1166.

    Not in our library10.1111/jdv.18301

  191. 191.

    Alpalhao, M. et al. Monkeypox: a new (sexually transmissible) epidemic? J. Eur. Acad. Dermatol. Venereol. 10.1111/jdv.18424 (2022).

    Not in our library10.1111/jdv.18424

  192. 192.

    Laurence, J. The recent rise in sexually transmitted infections in the United States was a harbinger of the new monkeypox pandemic. AIDS Patient Care STDS36, 333–335 (2022).

    Not in our library10.1089/apc.2022.29009.com

  193. 193.

    Curran KG, et al. HIV and sexually transmitted infections among persons with monkeypox - eight U.S. jurisdictions, May 17-July 22, 2022. MMWR Morb. Mortal. Wkly Rep. 2022;71:1141-1147.

    Not in our library10.15585/mmwr.mm7136a1

  194. 194.

    Hughes AL, Irausquin S, Friedman R. The evolutionary biology of poxviruses. Infect. Genet. Evol. 2010;10:50-59.

    Not in our library10.1016/j.meegid.2009.10.001

  195. 195.

    Mackett M, Archard LC. Conservation and variation in orthopoxvirus genome structure. J. Gen. Virol. 1979;45:683-701.

    Not in our library10.1099/0022-1317-45-3-683

  196. 196.

    Buller RM, Palumbo GJ. Poxvirus pathogenesis. Microbiol. Rev. 1991;55:80-122.

    Not in our library10.1128/mr.55.1.80-122.1991

  197. 197.

    Shchelkunov SN, et al. Analysis of the monkeypox virus genome. Virology. 2002;297:172-194.

    Not in our library10.1006/viro.2002.1446

  198. 198.

    Vandenbogaert M, et al. Nanopore sequencing of a monkeypox virus strain isolated from a pustular lesion in the Central African Republic. Sci. Rep. 2022;12:10768.

    Not in our library10.1038/s41598-022-15073-1

  199. 199.
    Orthopoxvirus Genome Evolution: The Role of Gene Loss · 2010
    No notice
  200. 200.
    Genomic Variability of Monkeypox Virus among Humans, Democratic Republic of the Congo · 2014
    No notice
  201. 201.

    Barry M, Wasilenko ST, Stewart TL, Taylor JM. Apoptosis regulator genes encoded by poxviruses. Prog. Mol. Subcell. Biol. 2004;36:19-37.

    Not in our library10.1007/978-3-540-74264-7_2

  202. 202.

    Seet BT, et al. Poxviruses and immune evasion. Annu. Rev. Immunol. 2003;21:377-423.

    Not in our library10.1146/annurev.immunol.21.120601.141049

  203. 203.

    Esteban DJ, Hutchinson AP. Genes in the terminal regions of orthopoxvirus genomes experience adaptive molecular evolution. BMC Genomics. 2011;12:261.

    Not in our library10.1186/1471-2164-12-261

  204. 204.

    Elde NC, et al. Poxviruses deploy genomic accordions to adapt rapidly against host antiviral defenses. Cell. 2012;150:831-841.

    Not in our library10.1016/j.cell.2012.05.049

  205. 205.

    Challberg MD, Englund PT. Purification and properties of the deoxyribonucleic acid polymerase induced by vaccinia virus. J. Biol. Chem. 1979;254:7812-7819.

    Not in our library10.1016/s0021-9258(18)36019-8

  206. 206.

    Firth C, et al. Using time-structured data to estimate evolutionary rates of double-stranded DNA viruses. Mol. Biol. Evol. 2010;27:2038-2051.

    Not in our library10.1093/molbev/msq088

  207. 207.

    O’Toole, A. & Rambaut, Á. Initial observations about putative APOBEC3 deaminase editing driving short-term evolution of MPXV since 2017. https://virological.org/t/initial-observations-about-putative-apobec3-deaminase-editing-driving-short-term-evolution-of-mpxv-since-2017/830 (2022).

    Not in our library

  208. 208.

    Pecori R, Di Giorgio S, Paulo Lorenzo J, Nina Papavasiliou F. Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination. Nat. Rev. Genet. 2022;23:505-518.

    Not in our library10.1038/s41576-022-00459-8

  209. 209.

    Sadeghpour, S. et al. Human APOBEC3 variations and viral infection. Viruses. 13, 1366 (2021).

    Not in our library10.3390/v13071366

  210. 210.

    Martinez T, Shapiro M, Bhaduri-McIntosh S, MacCarthy T. Evolutionary effects of the AID/APOBEC family of mutagenic enzymes on human gamma-herpesviruses. Virus Evol. 2019;5:vey040.

    Not in our library10.1093/ve/vey040

  211. 211.
    Likely Role of APOBEC3G-Mediated G-to-A Mutations in HIV-1 Evolution and Drug Resistance · 2009
    No notice
  212. 212.

    Kremer M, et al. Vaccinia virus replication is not affected by APOBEC3 family members. Virol. J. 2006;3:86.

    Not in our library10.1186/1743-422x-3-86

  213. 213.

    Wang, L. et al. Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022. J. Med. Virol. 10.1002/jmv.28036 (2022).

    Not in our library10.1002/jmv.28036

  214. 214.

    Moss B. Poxvirus entry and membrane fusion. Virology. 2006;344:48-54.

    Not in our library10.1016/j.virol.2005.09.037

  215. 215.

    Moss B. Membrane fusion during poxvirus entry. Semin. Cell Dev. Biol. 2016;60:89-96.

    Not in our library10.1016/j.semcdb.2016.07.015

  216. 216.

    Smith GL, Vanderplasschen A, Law M. The formation and function of extracellular enveloped vaccinia virus. J. Gen. Virol. 2002;83:2915-2931.

    Not in our library10.1099/0022-1317-83-12-2915

  217. 217.

    Schmidt FI, Bleck CK, Mercer J. Poxvirus host cell entry. Curr. Opin. Virol. 2012;2:20-27.

    Not in our library10.1016/j.coviro.2011.11.007

  218. 218.
    Entry of the Two Infectious Forms of Vaccinia Virus at the Plasma Membane Is Signaling-Dependent for the IMV but Not the EEV · 2000
    Not checked
  219. 219.

    Vanderplasschen A, Hollinshead M, Smith GL. Intracellular and extracellular vaccinia virions enter cells by different mechanisms. J. Gen. Virol. 1998;79(Pt. 4):877-887.

    Not in our library10.1099/0022-1317-79-4-877

  220. 220.

    Vanderplasschen A, Smith GL. A novel virus binding assay using confocal microscopy: demonstration that the intracellular and extracellular vaccinia virions bind to different cellular receptors. J. Virol. 1997;71:4032-4041.

    Not in our library10.1128/jvi.71.5.4032-4041.1997

  221. 221.

    Manes NP, et al. Comparative proteomics of human monkeypox and vaccinia intracellular mature and extracellular enveloped virions. J. Proteome Res. 2008;7:960-968.

    Not in our library10.1021/pr070432+

  222. 222.

    Smith GL, Law M. The exit of vaccinia virus from infected cells. Virus Res. 2004;106:189-197.

    Not in our library10.1016/j.virusres.2004.08.015

  223. 223.
    Poxvirus Cell Entry: How Many Proteins Does it Take? · 2012
    No notice
  224. 224.

    Chiu WL, et al. Vaccinia virus 4c (A26L) protein on intracellular mature virus binds to the extracellular cellular matrix laminin. J. Virol. 2007;81:2149-2157.

    Not in our library10.1128/jvi.02302-06

  225. 225.

    Matho MH, et al. Structure-function characterization of three human antibodies targeting the vaccinia virus adhesion molecule D8. J. Biol. Chem. 2018;293:390-401.

    Not in our library10.1074/jbc.m117.814541

  226. 226.

    Hsiao JC, Chung CS, Chang W. Vaccinia virus envelope D8L protein binds to cell surface chondroitin sulfate and mediates the adsorption of intracellular mature virions to cells. J. Virol. 1999;73:8750-8761.

    Not in our library10.1128/jvi.73.10.8750-8761.1999

  227. 227.

    Chung CS, Hsiao JC, Chang YS, Chang W. A27L protein mediates vaccinia virus interaction with cell surface heparan sulfate. J. Virol. 1998;72:1577-1585.

    Not in our library10.1128/jvi.72.2.1577-1585.1998

  228. 228.

    Berhanu A, et al. Vaccination of BALB/c mice with Escherichia coli-expressed vaccinia virus proteins A27L, B5R, and D8L protects mice from lethal vaccinia virus challenge. J. Virol. 2008;82:3517-3529.

    Not in our library10.1128/jvi.01854-07

  229. 229.

    Blasco R, Sisler JR, Moss B. Dissociation of progeny vaccinia virus from the cell membrane is regulated by a viral envelope glycoprotein: effect of a point mutation in the lectin homology domain of the A34R gene. J. Virol. 1993;67:3319-3325.

    Not in our library10.1128/jvi.67.6.3319-3325.1993

  230. 230.

    Thirunavukarasu P, et al. A rationally designed A34R mutant oncolytic poxvirus: improved efficacy in peritoneal carcinomatosis. Mol. Ther. 2013;21:1024-1033.

    Not in our library10.1038/mt.2013.27

  231. 231.

    Wolffe EJ, Katz E, Weisberg A, Moss B. The A34R glycoprotein gene is required for induction of specialized actin-containing microvilli and efficient cell-to-cell transmission of vaccinia virus. J. Virol. 1997;71:3904-3915.

    Not in our library10.1128/jvi.71.5.3904-3915.1997

  232. 232.

    McIntosh AA, Smith GL. Vaccinia virus glycoprotein A34R is required for infectivity of extracellular enveloped virus. J. Virol. 1996;70:272-281.

    Not in our library10.1128/jvi.70.1.272-281.1996

  233. 233.

    Lin CL, Chung CS, Heine HG, Chang W. Vaccinia virus envelope H3L protein binds to cell surface heparan sulfate and is important for intracellular mature virion morphogenesis and virus infection in vitro and in vivo. J. Virol. 2000;74:3353-3365.

    Not in our library10.1128/jvi.74.7.3353-3365.2000

  234. 234.

    Davies DH, et al. Vaccinia virus H3L envelope protein is a major target of neutralizing antibodies in humans and elicits protection against lethal challenge in mice. J. Virol. 2005;79:11724-11733.

    Not in our library10.1128/jvi.79.18.11724-11733.2005

  235. 235.

    da Fonseca FG, Wolffe EJ, Weisberg A, Moss B. Effects of deletion or stringent repression of the H3L envelope gene on vaccinia virus replication. J. Virol. 2000;74:7518-7528.

    Not in our library10.1128/jvi.74.16.7518-7528.2000

  236. 236.

    Foo CH, et al. Vaccinia virus L1 binds to cell surfaces and blocks virus entry independently of glycosaminoglycans. Virology. 2009;385:368-382.

    Not in our library10.1016/j.virol.2008.12.019

  237. 237.

    Townsley AC, Senkevich TG, Moss B. Vaccinia virus A21 virion membrane protein is required for cell entry and fusion. J. Virol. 2005;79:9458-9469.

    Not in our library10.1128/jvi.79.15.9458-9469.2005

  238. 238.

    Townsley AC, Senkevich TG, Moss B. The product of the vaccinia virus L5R gene is a fourth membrane protein encoded by all poxviruses that is required for cell entry and cell-cell fusion. J. Virol. 2005;79:10988-10998.

    Not in our library10.1128/jvi.79.17.10988-10998.2005

  239. 239.

    Senkevich TG, Moss B. Vaccinia virus H2 protein is an essential component of a complex involved in virus entry and cell-cell fusion. J. Virol. 2005;79:4744-4754.

    Not in our library10.1128/jvi.79.8.4744-4754.2005

  240. 240.

    Diesterbeck US, Gittis AG, Garboczi DN, Moss B. The 2.1 A structure of protein F9 and its comparison to L1, two components of the conserved poxvirus entry-fusion complex. Sci. Rep. 2018;8:16807.

    Not in our library10.1038/s41598-018-34244-7

  241. 241.
    The Membrane Fusion Step of Vaccinia Virus Entry Is Cooperatively Mediated by Multiple Viral Proteins and Host Cell Components · 2011
    No notice
  242. 242.

    Bisht H, Weisberg AS, Moss B. Vaccinia virus l1 protein is required for cell entry and membrane fusion. J. Virol. 2008;82:8687-8694.

    Not in our library10.1128/jvi.00852-08

  243. 243.

    Brown E, Senkevich TG, Moss B. Vaccinia virus F9 virion membrane protein is required for entry but not virus assembly, in contrast to the related L1 protein. J. Virol. 2006;80:9455-9464.

    Not in our library10.1128/jvi.01149-06

  244. 244.

    McFadden G. Poxvirus tropism. Nat. Rev. Microbiol. 2005;3:201-213.

    Not in our library10.1038/nrmicro1099

  245. 245.

    Wright CF, Hubbs AE, Gunasinghe SK, Oswald BW. A vaccinia virus late transcription factor copurifies with a factor that binds to a viral late promoter and is complemented by extracts from uninfected HeLa cells. J. Virol. 1998;72:1446-1451.

    Not in our library10.1128/jvi.72.2.1446-1451.1998

  246. 246.

    Sanz P, Moss B. A new vaccinia virus intermediate transcription factor. J. Virol. 1998;72:6880-6883.

    Not in our library10.1128/jvi.72.8.6880-6883.1998

  247. 247.

    Rosales R, Sutter G, Moss B. A cellular factor is required for transcription of vaccinia viral intermediate-stage genes. Proc. Natl Acad. Sci. USA. 1994;91:3794-3798.

    Not in our library10.1073/pnas.91.9.3794

  248. 248.

    Rosales R, Harris N, Ahn BY, Moss B. Purification and identification of a vaccinia virus-encoded intermediate stage promoter-specific transcription factor that has homology to eukaryotic transcription factor SII (TFIIS) and an additional role as a viral RNA polymerase subunit. J. Biol. Chem. 1994;269:14260-14267.

    Not in our library10.1016/s0021-9258(17)36783-2

  249. 249.

    Roberts KL, Smith GL. Vaccinia virus morphogenesis and dissemination. Trends Microbiol. 2008;16:472-479.

    Not in our library10.1016/j.tim.2008.07.009

  250. 250.

    Pauli G, et al. Orthopox viruses: infections in humans. Transfus. Med. Hemother. 2010;37:351-364.

    Not in our library10.1159/000322101

  251. 251.

    Nalca A, Rimoin AW, Bavari S, Whitehouse CA. Reemergence of monkeypox: prevalence, diagnostics, and countermeasures. Clin. Infect. Dis. 2005;41:1765-1771.

    Not in our library10.1086/498155

  252. 252.

    Breman JG, et al. Human monkeypox, 1970-79. Bull. World Health Organ. 1980;58:165-182.

    Not in our library

  253. 253.

    Mahase E. Monkeypox: what do we know about the outbreaks in Europe and North America? BMJ. 2022;377:o1274.

    Not in our library10.1136/bmj.o1274

  254. 254.

    Petersen E, et al. Human monkeypox: epidemiologic and clinical characteristics, diagnosis, and prevention. Infect. Dis. Clin. North Am. 2019;33:1027-1043.

    Not in our library10.1016/j.idc.2019.03.001

  255. 255.
    Estimated incubation period for monkeypox cases confirmed in the Netherlands, May 2022 · 2022
    Corrected
  256. 256.

    Charniga, K. et al. Estimating the incubation period of monkeypox virus during the 2022. Preprint at medRxiv10.1101/2022.06.22.22276713 (2022).

    Not in our library

  257. 257.

    WHO. Monkeypox (World Health Organization, 2022).

    Not in our library

  258. 258.

    Cheema AY, et al. Monkeypox: a review of clinical features, diagnosis, and treatment. Cureus. 2022;14:e26756.

    Not in our library10.7759/cureus.26756

  259. 259.

    PR Pittman et al. Clinical characterization of human monkeypox infections in the Democratic Republic of the Congo. medRxiv, (2022).

    Not in our library

  260. 260.
    Clinical features, hospitalisation and deaths associated with monkeypox: a systematic review and meta-analysis · 2022
    Not checked
  261. 261.

    McCollum AM, Damon IK. Human monkeypox. Clin. Infect. Dis. 2014;58:260-267.

    Not in our library10.1093/cid/cit703

  262. 262.

    Singhal, T., Kabra, S. K. & Lodha, R. Monkeypox: a review. Indian J. Pediatr. 89, 955–960 (2022).

    Not in our library10.1007/s12098-022-04348-0

  263. 263.

    Saxena, S. K. et al. Re-emerging human monkeypox: a major public-health debacle. J. Med. Virol.10.1002/jmv.27902 (2022).

    Not in our library10.1002/jmv.27902

  264. 264.

    Patrocinio-Jesus R, Peruzzu F. Monkeypox genital lesions. N. Engl. J. Med. 2022;387:66.

    Not in our library10.1056/nejmicm2206893

  265. 265.

    Portela-Dias, J., Sereno, S., Falcao-Reis, I. & Rasteiro, C. Monkeypox infection with localized genital lesions in women. Am. J. Obstet. Gynecol. 10.1016/j.ajog.2022.08.046 (2022).

    Not in our library10.1016/j.ajog.2022.08.046

  266. 266.

    Paparizos, V. et al. Monkeypox virus infection: first reported case in Greece in a patient with a genital rash. J. Eur. Acad. Dermatol. Venereol. 10.1111/jdv.18521 (2022).

    Not in our library10.1111/jdv.18521

  267. 267.
    Monkeypox infection presenting as genital rash, Australia, May 2022 · 2022
    No notice
  268. 268.

    Griffiths-Acha, J., Vela-Ganuza, M., Sarro-Fuente, C. & Lopez-Estebaranz, J. L. Monkeypox: a new differential diagnosis when addressing genital ulcer disease. Br. J. Dermatol.10.1111/bjd.21834 (2022).

    Not in our library10.1111/bjd.21834

  269. 269.

    Davido, B. et al. Monkeypox 2022 outbreak: cases with exclusive genital lesions. J. Travel Med. 29, taac077 (2022).

    Not in our library10.1093/jtm/taac077

  270. 270.

    Bociaga-Jasik, M. et al. Monkeypox present with genital ulcers-challenging clinical problem. Pol. Arch. Intern. Med.10.20452/pamw.16304 (2022).

    Not in our library10.20452/pamw.16304

  271. 271.

    Girometti, N. et al. Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis. Lancet Infect. Dis.28, 1321–1328 (2022).

    Not in our library10.1016/s1473-3099(22)00411-x

  272. 272.

    Patel A, et al. Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series. BMJ. 2022;378:e072410.

    Not in our library10.1136/bmj-2022-072410

  273. 273.

    Abbasi, J. Reports of asymptomatic monkeypox suggest that, at the very least, some infections go unnoticed. JAMA328, 1023–1025 (2022).

    Not in our library10.1001/jama.2022.15426

  274. 274.
    Ongoing monkeypox virus outbreak, Portugal, 29 April to 23 May 2022 · 2022
    No notice
  275. 275.

    Adalja, A. & Inglesby, T. A novel international monkeypox outbreak. Ann. Intern. Med.175, 1175–1176 (2022).

    Not in our library10.7326/m22-1581

  276. 276.

    Kumbhar, N. & Agarwala, P. The lurking threat of monkeypox in current times. Indian J. Med. Microbiol. 10.1016/j.ijmmb.2022.07.016 (2022).

    Not in our library10.1016/j.ijmmb.2022.07.016

  277. 277.

    Kindrachuk, J. et al. Systems kinomics demonstrates Congo Basin monkeypox virus infection selectively modulates host cell signaling responses as compared to West African monkeypox virus. Mol. Cell. Proteomics10.1074/mcp.M111.015701 (2012).

    Not in our library10.1074/mcp.m111.015701

  278. 278.

    Li Y, et al. Real-time PCR assays for the specific detection of monkeypox virus West African and Congo Basin strain DNA. J. Virol. Methods. 2010;169:223-227.

    Not in our library10.1016/j.jviromet.2010.07.012

  279. 279.

    See, K. C. Vaccination for monkeypox virus infection in humans: a review of key considerations. Vaccines10, 1342 (2022).

    Not in our library10.3390/vaccines10081342

  280. 280.

    WHO. Laboratory testing for the monkeypox virus: Interim guidance. https://www.who.int/publications/i/item/WHO-MPX-laboratory-2022.1 (2022).

    Not in our library

  281. 281.

    Ropp SL, et al. PCR strategy for identification and differentiation of small pox and other orthopoxviruses. J. Clin. Microbiol. 1995;33:2069-2076.

    Not in our library10.1128/jcm.33.8.2069-2076.1995

  282. 282.

    Meyer H, Ropp SL, Esposito JJ. Gene for A-type inclusion body protein is useful for a polymerase chain reaction assay to differentiate orthopoxviruses. J. Virol. Methods. 1997;64:217-221.

    Not in our library10.1016/s0166-0934(96)02155-6

  283. 283.

    Neubauer H, et al. Specific detection of monkeypox virus by polymerase chain reaction. J. Virol. Methods. 1998;74:201-207.

    Not in our library10.1016/s0166-0934(98)00099-8

  284. 284.

    Loparev VN, Massung RF, Esposito JJ, Meyer H. Detection and differentiation of old world orthopoxviruses: restriction fragment length polymorphism of the crmB gene region. J. Clin. Microbiol. 2001;39:94-100.

    Not in our library10.1128/jcm.39.1.94-100.2001

  285. 285.

    Li Y, et al. Detection of monkeypox virus with real-time PCR assays. J. Clin. Virol. 2006;36:194-203.

    Not in our library10.1016/j.jcv.2006.03.012

  286. 286.

    Shchelkunov SN, Shcherbakov DN, Maksyutov RA, Gavrilova EV. Species-specific identification of variola, monkeypox, cowpox, and vaccinia viruses by multiplex real-time PCR assay. J. Virol. Methods. 2011;175:163-169.

    Not in our library10.1016/j.jviromet.2011.05.002

  287. 287.
    Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022 · 2022
    No notice
  288. 288.

    Orba Y, et al. Orthopoxvirus infection among wildlife in Zambia. J. Gen. Virol. 2015;96:390-394.

    Not in our library10.1099/vir.0.070219-0

  289. 289.

    Kulesh DA, et al. Monkeypox virus detection in rodents using real-time 3’-minor groove binder TaqMan assays on the Roche LightCycler. Lab. Invest. 2004;84:1200-1208.

    Not in our library10.1038/labinvest.3700143

  290. 290.

    Davi SD, et al. Recombinase polymerase amplification assay for rapid detection of Monkeypox virus. Diagn. Microbiol. Infect. Dis. 2019;95:41-45.

    Not in our library10.1016/j.diagmicrobio.2019.03.015

  291. 291.

    Jiang Z, et al. Laboratory diagnostics for monkeypox: an overview of sensitivities from various published tests. Travel Med. Infect. Dis. 2022;49:102425.

    Not in our library10.1016/j.tmaid.2022.102425

  292. 292.

    Maksyutov RA, Gavrilova EV, Shchelkunov SN. Species-specific differentiation of variola, monkeypox, and varicella-zoster viruses by multiplex real-time PCR assay. J. Virol. Methods. 2016;236:215-220.

    Not in our library10.1016/j.jviromet.2016.07.024

  293. 293.

    Norz, D. et al. Rapid adaptation of established high-throughput molecular testing infrastructure for monkeypox virus detection. Emerg. Infect. Dis. 28, 1765–1769 (2022).

    Not in our library10.3201/eid2809.220917

  294. 294.

    Scaramozzino N, et al. Real-time PCR to identify variola virus or other human pathogenic orthopox viruses. Clin. Chem. 2007;53:606-613.

    Not in our library10.1373/clinchem.2006.068635

  295. 295.

    Ulaeto, D. O., Dunning, J. & Carroll, M. W. Evolutionary implications of human transmission of monkeypox: the importance of sequencing multiple lesions. Lancet Microbe3, e639–e640 (2022).

    Not in our library10.1016/s2666-5247(22)00194-x

  296. 296.

    Iizuka I, et al. Loop-mediated isothermal amplification-based diagnostic assay for monkeypox virus infections. J. Med. Virol. 2009;81:1102-1108.

    Not in our library10.1002/jmv.21494

  297. 297.

    Dumont C, et al. Simple technique for in field samples collection in the cases of skin rash illness and subsequent PCR detection of orthopoxviruses and varicella zoster virus. PLoS ONE. 2014;9:e96930.

    Not in our library10.1371/journal.pone.0096930

  298. 298.

    Hammarlund E, et al. Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox. Nat. Med. 2005;11:1005-1011.

    Not in our library10.1038/nm1273

  299. 299.

    Dubois ME, Hammarlund E, Slifka MK. Optimization of peptide-based ELISA for serological diagnostics: a retrospective study of human monkeypox infection. Vector Borne Zoonotic Dis. 2012;12:400-409.

    Not in our library10.1089/vbz.2011.0779

  300. 300.

    Fernandez de Marco Mdel M, et al. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon. FASEB J. 2010;24:1479-1488.

    Not in our library10.1096/fj.09-144733

  301. 301.

    Sejvar JJ, et al. Human monkeypox infection: a family cluster in the midwestern United States. J. Infect. Dis. 2004;190:1833-1840.

    Not in our library10.1086/425039

  302. 302.

    Karem KL, et al. characterization of acute-phase humoral immunity to monkeypox: use of immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox infection during the 2003 North American outbreak. Clin. Diagn. Lab. Immunol. 2005;12:867-872.

    Not in our library10.1128/cdli.12.7.867-872.2005

  303. 303.

    Stagles MJ, et al. The histopathology and electron microscopy of a human monkeypox lesion. Trans. R. Soc. Trop. Med. Hyg. 1985;79:192-202.

    Not in our library10.1016/0035-9203(85)90333-5

  304. 304.

    Sherwat, A., Brooks, J. T., Birnkrant, D. & Kim, P. Tecovirimat and the treatment of monkeypox - past, present, and future considerations. N. Engl. J. Med.387, 579–581 (2022).

    Not in our library10.1056/nejmp2210125

  305. 305.

    Rizk JG, et al. Prevention and treatment of monkeypox. Drugs. 2022;82:957-963.

    Not in our library10.1007/s40265-022-01742-y

  306. 306.

    O’Shea J, et al. Interim guidance for prevention and treatment of monkeypox in persons with HIV infection - United States, August 2022. MMWR Morb. Mortal. Wkly Rep. 2022;71:1023-1028.

    Not in our library10.15585/mmwr.mm7132e4

  307. 307.

    Goyal L, Ajmera K, Pandit R, Pandit T. Prevention and treatment of monkeypox: a step-by-step guide for healthcare professionals and general population. Cureus. 2022;14:e28230.

    Not in our library10.7759/cureus.28230

  308. 308.

    Desai, A. N. et al. Compassionate use of tecovirimat for the treatment of monkeypox infection. JAMA328, 1348–1350 (2022).

    Not in our library10.1001/jama.2022.15336

  309. 309.

    Yang G, et al. An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus challenge. J. Virol. 2005;79:13139-13149.

    Not in our library10.1128/jvi.79.20.13139-13149.2005

  310. 310.

    Jordan R, et al. ST-246 antiviral efficacy in a nonhuman primate monkeypox model: determination of the minimal effective dose and human dose justification. Antimicrob. Agents Chemother. 2009;53:1817-1822.

    Not in our library10.1128/aac.01596-08

  311. 311.

    Kabanov AS, et al. A comparative study of the antiviral activity of chemical compounds concerning the orthopoxviruses experiments in vivo. Vopr. Virusol. 2013;58:39-43.

    Not in our library

  312. 312.

    Smith SK, et al. In vitro efficacy of ST246 against smallpox and monkeypox. Antimicrob. Agents Chemother. 2009;53:1007-1012.

    Not in our library10.1128/aac.01044-08

  313. 313.

    Bolken TC, Hruby DE. Tecovirimat for smallpox infections. Drugs Today. 2010;46:109-117.

    Not in our library10.1358/dot.2010.46.2.1437244

  314. 314.
    Historical Perspectives in the Development of Antiviral Agents Against Poxviruses · 2010
    Not checked
  315. 315.

    Blasco R, Moss B. Extracellular vaccinia virus formation and cell-to-cell virus transmission are prevented by deletion of the gene encoding the 37,000-Dalton outer envelope protein. J. Virol. 1991;65:5910-5920.

    Not in our library10.1128/jvi.65.11.5910-5920.1991

  316. 316.

    Vliegen I, et al. Deletion of the vaccinia virus F13L gene results in a highly attenuated virus that mounts a protective immune response against subsequent vaccinia virus challenge. Antivir. Res. 2012;93:160-166.

    Not in our library10.1016/j.antiviral.2011.11.010

  317. 317.

    Duraffour S, et al. ST-246 is a key antiviral to inhibit the viral F13L phospholipase, one of the essential proteins for orthopoxvirus wrapping. J. Antimicrob. Chemother. 2015;70:1367-1380.

    Not in our library10.1093/jac/dku545

  318. 318.

    Frenois-Veyrat, G. et al. Tecovirimat is highly efficient on the Monkeypox virus lineage responsible for the international 2022 outbreak. Preprint at bioRxiv10.1101/2022.07.19.500484 (2022).

    Not in our library

  319. 319.

    Sbrana E, et al. Efficacy of the antipoxvirus compound ST-246 for treatment of severe orthopoxvirus infection. Am. J. Trop. Med. Hyg. 2007;76:768-773.

    Not in our library10.4269/ajtmh.2007.76.768

  320. 320.

    Quenelle DC, et al. Efficacy of delayed treatment with ST-246 given orally against systemic orthopoxvirus infections in mice. Antimicrob. Agents Chemother. 2007;51:689-695.

    Not in our library10.1128/aac.00879-06

  321. 321.

    Russo AT, et al. Effects of treatment delay on efficacy of tecovirimat following lethal aerosol monkeypox virus challenge in cynomolgus macaques. J. Infect. Dis. 2018;218:1490-1499.

    Not in our library10.1093/infdis/jiy326

  322. 322.

    Delaune, D. & Iseni, F. Drug development against smallpox: present and future. Antimicrob. Agents Chemother. 64, e01683-19 (2020).

    Not in our library10.1128/aac.01683-19

  323. 323.

    Laudisoit A, Tepage F, Colebunders R. Oral tecovirimat for the treatment of smallpox. N. Engl. J. Med. 2018;379:2084-2085.

    Not in our library10.1056/nejmc1811044

  324. 324.

    Grosenbach DW, et al. Oral tecovirimat for the treatment of smallpox. N. Engl. J. Med. 2018;379:44-53.

    Not in our library10.1056/nejmoa1705688

  325. 325.

    Huggins J, et al. Nonhuman primates are protected from smallpox virus or monkeypox virus challenges by the antiviral drug ST-246. Antimicrob. Agents Chemother. 2009;53:2620-2625.

    Not in our library10.1128/aac.00021-09

  326. 326.

    Smith SK, et al. Effective antiviral treatment of systemic orthopoxvirus disease: ST-246 treatment of prairie dogs infected with monkeypox virus. J. Virol. 2011;85:9176-9187.

    Not in our library10.1128/jvi.02173-10

  327. 327.

    Berhanu A, et al. Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection. Antimicrob. Agents Chemother. 2015;59:4296-4300.

    Not in our library10.1128/aac.00208-15

  328. 328.

    Wang, X. et al. Effects of adjuvants on the immunogenicity and efficacy of a zika virus envelope domain III subunit vaccine. Vaccines7, 161 (2019).

    Not in our library10.3390/vaccines7040161

  329. 329.

    Adler H, et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect. Dis. 2022;22:1153-1162.

    Not in our library10.1016/s1473-3099(22)00228-6

  330. 330.

    Peters, S. M., Hill, N. B. & Halepas, S. Oral manifestations of monkeypox: a report of 2 cases. J. Oral Maxillofac. Surg.10.1016/j.joms.2022.07.147 (2022).

    Not in our library10.1016/j.joms.2022.07.147

  331. 331.

    Matias WR, et al. Tecovirimat for the treatment of human monkeypox: an initial series from Massachusetts, United States. Open Forum Infect. Dis. 2022;9:ofac377.

    Not in our library10.1093/ofid/ofac377

  332. 332.

    Lucar, J. et al. Monkeypox virus-associated severe proctitis treated with oral tecovirimat: a report of two cases. Ann. Intern. Med.10.7326/L22-0300 (2022).

    Not in our library10.7326/l22-0300

  333. 333.

    CDC. Demographics of patients receiving TPOXX for treatment of monkeypox. https://www.cdc.gov/poxvirus/monkeypox/response/2022/demographics-TPOXX.html (2022).

    Not in our library

  334. 334.

    Nakoune E, Olliaro P. Waking up to monkeypox. BMJ. 2022;377:o1321.

    Not in our library10.1136/bmj.o1321

  335. 335.

    FACT SHEET: Ongoing U.S. monkeypox research activities to speed science for impact. https://www.whitehouse.gov/ostp/news-updates/2022/08/11/fact-sheet-ongoing-u-s-monkeypox-research-activities-to-speed-science-for-impact/ (2022).

    Not in our library

  336. 336.

    Del Rio, C. & Malani, P. N. Update on the monkeypox outbreak. JAMA328, 921–922 (2022).

    Not in our library10.1001/jama.2022.14857

  337. 337.

    Harris E. Global monkeypox outbreaks spur drug research for the neglected disease. JAMA. 2022;328:231-233.

    Not in our library10.1001/jama.2022.11224

  338. 338.

    De Clercq E. Cidofovir in the treatment of poxvirus infections. Antivir. Res. 2002;55:1-13.

    Not in our library10.1016/s0166-3542(02)00008-6

  339. 339.

    Cidofovir approved. PI Perspect 14–15 (1996).

    Not in our library

  340. 340.

    FDA panel unanimously recommends approval of Vistide for CMV retinitis. Food and Drug Administration. J. Int. Assoc. Physicians AIDS Care. 2, 50 (1996).

    Not in our library

  341. 341.

    FDA grants marketing clearance of Vistide for the treatment of CMV retinitis. AIDS Patient Care STDS. 10, 383–384 (1996).

    Not in our library

  342. 342.

    Hostetler KY. Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art. Antivir. Res. 2009;82:A84-98.

    Not in our library10.1016/j.antiviral.2009.01.005

  343. 343.

    Magee WC, Hostetler KY, Evans DH. Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate. Antimicrob. Agents Chemother. 2005;49:3153-3162.

    Not in our library10.1128/aac.49.8.3153-3162.2005

  344. 344.

    Aldern KA, Ciesla SL, Winegarden KL, Hostetler KY. Increased antiviral activity of 1-O-hexadecyloxypropyl-[2-(14)C]cidofovir in MRC-5 human lung fibroblasts is explained by unique cellular uptake and metabolism. Mol. Pharmacol. 2003;63:678-681.

    Not in our library10.1124/mol.63.3.678

  345. 345.
    Cidofovir Activity against Poxvirus Infections · 2010
    No notice
  346. 346.

    Neyts J, Leyssen P, Verbeken E, De Clercq E. Efficacy of cidofovir in a murine model of disseminated progressive vaccinia. Antimicrob. Agents Chemother. 2004;48:2267-2273.

    Not in our library10.1128/aac.48.6.2267-2273.2004

  347. 347.

    Smee DF, et al. Characterization of wild-type and cidofovir-resistant strains of camelpox, cowpox, monkeypox, and vaccinia viruses. Antimicrob. Agents Chemother. 2002;46:1329-1335.

    Not in our library10.1128/aac.46.5.1329-1335.2002

  348. 348.

    Yu, J. & Raj, S. M. Efficacy of three key antiviral drugs used to treat orthopoxvirus infections: a systematic review. Glob. Biosecurity10.31646/gbio.12 (2019).

    Not in our library

  349. 349.

    Baker RO, Bray M, Huggins JW. Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections. Antivir. Res. 2003;57:13-23.

    Not in our library10.1016/s0166-3542(02)00196-1

  350. 350.

    Robbins SJ, et al. The efficacy of cidofovir treatment of mice infected with ectromelia (mousepox) virus encoding interleukin-4. Antivir. Res. 2005;66:1-7.

    Not in our library10.1016/j.antiviral.2004.12.003

  351. 351.

    Quenelle DC, Collins DJ, Kern ER. Efficacy of multiple- or single-dose cidofovir against vaccinia and cowpox virus infections in mice. Antimicrob. Agents Chemother. 2003;47:3275-3280.

    Not in our library10.1128/aac.47.10.3275-3280.2003

  352. 352.

    Smee DF, et al. Differential pathogenesis of cowpox virus intranasal infections in mice induced by low and high inoculum volumes and effects of cidofovir treatment. Int. J. Antimicrob. Agents. 2008;31:352-359.

    Not in our library10.1016/j.ijantimicag.2007.11.013

  353. 353.

    Stittelaar KJ, et al. Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection. Nature. 2006;439:745-748.

    Not in our library10.1038/nature04295

  354. 354.

    Meadows KP, Tyring SK, Pavia AT, Rallis TM. Resolution of recalcitrant molluscum contagiosum virus lesions in human immunodeficiency virus-infected patients treated with cidofovir. Arch. Dermatol. 1997;133:987-990.

    Not in our library10.1001/archderm.1997.03890440061010

  355. 355.

    Davies EG, Thrasher A, Lacey K, Harper J. Topical cidofovir for severe molluscum contagiosum. Lancet. 1999;353:2042.

    Not in our library10.1016/s0140-6736(99)01782-1

  356. 356.

    Toro JR, Wood LV, Patel NK, Turner ML. Topical cidofovir: a novel treatment for recalcitrant molluscum contagiosum in children infected with human immunodeficiency virus 1. Arch. Dermatol. 2000;136:983-985.

    Not in our library10.1001/archderm.136.8.983

  357. 357.

    Vora S, et al. Severe eczema vaccinatum in a household contact of a smallpox vaccinee. Clin. Infect. Dis. 2008;46:1555-1561.

    Not in our library10.1086/587668

  358. 358.

    Graef S, et al. Clinicopathological findings in persistent corneal cowpox infection. JAMA Ophthalmol. 2013;131:1089-1091.

    Not in our library10.1001/jamaophthalmol.2013.264

  359. 359.

    Becker C, et al. Cowpox virus infection in pet rat owners: not always immediately recognized. Dtsch Arztebl Int. 2009;106:329-334.

    Not in our library10.3238/arztebl.2009.0329

  360. 360.

    Cihlar T, Chen MS. Identification of enzymes catalyzing two-step phosphorylation of cidofovir and the effect of cytomegalovirus infection on their activities in host cells. Mol. Pharmacol. 1996;50:1502-1510.

    Not in our library

  361. 361.

    Xiong X, Smith JL, Chen MS. Effect of incorporation of cidofovir into DNA by human cytomegalovirus DNA polymerase on DNA elongation. Antimicrob. Agents Chemother. 1997;41:594-599.

    Not in our library10.1128/aac.41.3.594

  362. 362.

    Magee WC, Aldern KA, Hostetler KY, Evans DH. Cidofovir and (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine are highly effective inhibitors of vaccinia virus DNA polymerase when incorporated into the template strand. Antimicrob Agents Chemother. 2008;52:586-597.

    Not in our library10.1128/aac.01172-07

  363. 363.

    Kinchington PR, et al. Sequence changes in the human adenovirus type 5 DNA polymerase associated with resistance to the broad spectrum antiviral cidofovir. Antivir. Res. 2002;56:73-84.

    Not in our library10.1016/s0166-3542(02)00098-0

  364. 364.

    Chou S, et al. Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus. J. Infect. Dis. 2003;188:32-39.

    Not in our library10.1086/375743

  365. 365.

    Florescu DF, Keck MA. Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses. Expert Rev. Antiinfect. Ther. 2014;12:1171-1178.

    Not in our library10.1586/14787210.2014.948847

  366. 366.
    Development of CMX001 for the Treatment of Poxvirus Infections · 2010
    No notice
  367. 367.

    Duraffour S, et al. Emergence of cowpox: study of the virulence of clinical strains and evaluation of antivirals. PLoS ONE. 2013;8:e55808.

    Not in our library10.1371/journal.pone.0055808

  368. 368.

    Parker S, et al. Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox. Antivir. Res. 2012;94:44-53.

    Not in our library10.1016/j.antiviral.2012.02.005

  369. 369.

    Rice AD, et al. Efficacy of CMX001 as a prophylactic and presymptomatic antiviral agent in New Zealand white rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans. Viruses. 2011;3:63-82.

    Not in our library10.3390/v3020063

  370. 370.

    Quenelle DC, et al. Oral treatment of cowpox and vaccinia virus infections in mice with ether lipid esters of cidofovir. Antimicrob. Agents Chemother. 2004;48:404-412.

    Not in our library10.1128/aac.48.2.404-412.2004

  371. 371.

    Quenelle DC, Kern ER. Treatment of vaccinia and cowpox virus infections in mice with CMX001 and ST-246. Viruses. 2010;2:2681-2695.

    Not in our library10.3390/v2122681

  372. 372.
    Ectromelia Virus Infections of Mice as a Model to Support the Licensure of Anti-Orthopoxvirus Therapeutics · 2010
    Not checked
  373. 373.

    Quenelle DC, et al. Efficacy of CMX001 against herpes simplex virus infections in mice and correlations with drug distribution studies. J. Infect. Dis. 2010;202:1492-1499.

    Not in our library10.1086/656717

  374. 374.

    Parker S, et al. Efficacy of therapeutic intervention with an oral ether-lipid analogue of cidofovir (CMX001) in a lethal mousepox model. Antivir. Res. 2008;77:39-49.

    Not in our library10.1016/j.antiviral.2007.08.003

  375. 375.

    Stabenow J, et al. A mouse model of lethal infection for evaluating prophylactics and therapeutics against Monkeypox virus. J. Virol. 2010;84:3909-3920.

    Not in our library10.1128/jvi.02012-09

  376. 376.

    Grossi IM, et al. Efficacy of delayed brincidofovir treatment against a lethal rabbitpox virus challenge in New Zealand White rabbits. Antivir. Res. 2017;143:278-286.

    Not in our library10.1016/j.antiviral.2017.04.002

  377. 377.

    Trost LC, et al. The efficacy and pharmacokinetics of brincidofovir for the treatment of lethal rabbitpox virus infection: a model of smallpox disease. Antivir. Res. 2015;117:115-121.

    Not in our library10.1016/j.antiviral.2015.02.007

  378. 378.

    Xiao SY, et al. Experimental infection of prairie dogs with monkeypox virus. Emerg. Infect. Dis. 2005;11:539-545.

    Not in our library10.3201/eid1104.040907

  379. 379.

    Weiner ZP, et al. Characterization of Monkeypox virus dissemination in the black-tailed prairie dog (Cynomys ludovicianus) through in vivo bioluminescent imaging. PLoS ONE. 2019;14:e0222612.

    Not in our library10.1371/journal.pone.0222612

  380. 380.

    Hutson, C. L. et al. Pharmacokinetics and efficacy of a potential smallpox therapeutic, brincidofovir, in a lethal monkeypox virus animal model. mSphere. 6, (2021).

    Not in our library10.1128/msphere.00927-20

  381. 381.

    Crump R, Korom M, Buller RM, Parker S. Buccal viral DNA as a trigger for brincidofovir therapy in the mousepox model of smallpox. Antivir. Res. 2017;139:112-116.

    Not in our library10.1016/j.antiviral.2016.12.015

  382. 382.

    Guarner J, Del Rio C, Malani PN. Monkeypox in 2022-what clinicians need to know. JAMA. 2022;328:139-140.

    Not in our library10.1001/jama.2022.10802

  383. 383.

    Hiwarkar P, et al. Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant. Blood. 2017;129:2033-2037.

    Not in our library10.1182/blood-2016-11-749721

  384. 384.

    Rice AD, et al. Efficacy of CMX001 as a post exposure antiviral in New Zealand White rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans. Viruses. 2011;3:47-62.

    Not in our library10.3390/v3010047

  385. 385.

    Sudhindra P, et al. Brincidofovir (CMX001) for the treatment of severe adenoviral pneumonia in kidney transplant recipient. Cureus. 2019;11:e5296.

    Not in our library10.7759/cureus.5296

  386. 386.

    Tippin TK, Morrison ME, Brundage TM, Mommeja-Marin H. Brincidofovir Is Not A Substrate For The Human Organic Anion Transporter 1: A Mechanistic Explanation For The Lack Of Nephrotoxicity Observed In Clinical Studies. Ther. Drug Monit. 2016;38:777-786.

    Not in our library10.1097/ftd.0000000000000353

  387. 387.

    Olson VA, et al. In vitro efficacy of brincidofovir against variola virus. Antimicrob. Agents Chemother. 2014;58:5570-5571.

    Not in our library10.1128/aac.02814-14

  388. 388.

    Lederman ER, et al. Progressive vaccinia: case description and laboratory-guided therapy with vaccinia immune globulin, ST-246, and CMX001. J. Infect. Dis. 2012;206:1372-1385.

    Not in our library10.1093/infdis/jis510

  389. 389.

    FDA. Vaccinia IMMUNE GLOBULIN INTRAVENOUS (HUMan). https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/vaccinia-immune-globulin-intravenous-human (2018).

    Not in our library

  390. 390.

    Wittek R. Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy. Int. J. Infect. Dis. 2006;10:193-201.

    Not in our library10.1016/j.ijid.2005.12.001

  391. 391.

    Whitehouse ER, et al. Novel treatment of a vaccinia virus infection from an occupational needlestick - San Diego, California, 2019. MMWR Morb. Mortal. Wkly Rep. 2019;68:943-946.

    Not in our library10.15585/mmwr.mm6842a2

  392. 392.

    Lindholm DA, et al. Preemptive tecovirimat use in an active duty service member who presented with acute myeloid leukemia after smallpox vaccination. Clin. Infect. Dis. 2019;69:2205-2207.

    Not in our library10.1093/cid/ciz286

  393. 393.

    Centers for Disease Control & Prevention. Human vaccinia infection after contact with a raccoon rabies vaccine bait -Pennsylvania, 2009. MMWR Morb. Mortal. Wkly Rep. 58, 1204–1207 (2009).

    Not in our library

  394. 394.

    Gilchuk I, et al. Cross-neutralizing and protective human antibody specificities to poxvirus infections. Cell. 2016;167:684.e9-694.e9.

    Not in our library10.1016/j.cell.2016.09.049

  395. 395.

    Edghill-Smith Y, et al. Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus. Nat. Med. 2005;11:740-747.

    Not in our library10.1038/nm1261

  396. 396.

    Stanford MM, McFadden G, Karupiah G, Chaudhri G. Immunopathogenesis of poxvirus infections: forecasting the impending storm. Immunol. Cell Biol. 2007;85:93-102.

    Not in our library10.1038/sj.icb.7100033

  397. 397.

    Ichihashi Y, Oie M. Epitope mosaic on the surface proteins of orthopoxviruses. Virology. 1988;163:133-144.

    Not in our library10.1016/0042-6822(88)90240-1

  398. 398.

    McConnell S, et al. Protection of rhesus monkeys against monkeypox by vaccinia virus immunization. Am. J. Vet. Res. 1964;25:192-195.

    Not in our library

  399. 399.

    Rao AK, et al. Use of JYNNEOS (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb. Mortal. Wkly Rep. 2022;71:734-742.

    Not in our library10.15585/mmwr.mm7122e1

  400. 400.

    Petersen E, et al. Vaccination for monkeypox prevention in persons with high-risk sexual behaviours to control on-going outbreak of monkeypox virus clade 3. Int. J. Infect. Dis. 2022;122:569-571.

    Not in our library10.1016/j.ijid.2022.06.047

  401. 401.

    Kupferschmidt K. Monkeypox vaccination plans take shape amid questions. Science. 2022;376:1142-1143.

    Not in our library10.1126/science.add3743

  402. 402.

    Kozlov M. Monkeypox vaccination begins - can the global outbreaks be contained? Nature. 2022;606:444-445.

    Not in our library10.1038/d41586-022-01587-1

  403. 403.

    Chakraborty, S. et al. Monkeypox vaccines and vaccination strategies: Current knowledge and advances. An update - correspondence. Int. J. Surg, 105, 106869 (2022).

    Not in our library10.1016/j.ijsu.2022.106869

  404. 404.

    Brooks, J. T., Marks, P., Goldstein, R. H. & Walensky, R. P. Intradermal vaccination for monkeypox - benefits for individual and public health. N. Engl. J. Med.387, 1151–1153 (2022).

    Not in our library10.1056/nejmp2211311

  405. 405.

    Erratum: Use of JYNNEOS (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb. Mortal. Wkly Rep. 71, 886 (2022).

    Not in our library10.15585/mmwr.mm7122e1

  406. 406.

    Jezek Z, et al. Human monkeypox: a study of 2,510 contacts of 214 patients. J. Infect. Dis. 1986;154:551-555.

    Not in our library10.1093/infdis/154.4.551

  407. 407.

    Rimoin AW, et al. Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proc. Natl Acad. Sci. USA. 2010;107:16262-16267.

    Not in our library10.1073/pnas.1005769107

  408. 408.

    Greenberg RN, Kennedy JS. ACAM2000: a newly licensed cell culture-based live vaccinia smallpox vaccine. Expert Opin. Investig. Drugs. 2008;17:555-564.

    Not in our library10.1517/13543784.17.4.555

  409. 409.

    Nalca A, Zumbrun EE. ACAM2000: the new smallpox vaccine for United States strategic national stockpile. Drug Des. Dev. Ther. 2010;4:71-79.

    Not in our library10.2147/dddt.s3687

  410. 410.

    Hatch GJ, et al. Assessment of the protective effect of Imvamune and Acam2000 vaccines against aerosolized monkeypox virus in cynomolgus macaques. J. Virol. 2013;87:7805-7815.

    Not in our library10.1128/jvi.03481-12

  411. 411.

    Keckler, M. S. et al. IMVAMUNE((R)) and ACAM2000((R)) provide different protection against disease when administered postexposure in an intranasal monkeypox challenge prairie dog model. Vaccines8, 396 (2020).

    Not in our library10.3390/vaccines8030396

  412. 412.

    Russo AT, et al. Co-administration of tecovirimat and ACAM2000 in non-human primates: Effect of tecovirimat treatment on ACAM2000 immunogenicity and efficacy versus lethal monkeypox virus challenge. Vaccine. 2020;38:644-654.

    Not in our library10.1016/j.vaccine.2019.10.049

  413. 413.

    Reed JL, Scott DE, Bray M. Eczema vaccinatum. Clin. Infect. Dis. 2012;54:832-840.

    Not in our library10.1093/cid/cir952

  414. 414.

    Cassimatis DC, et al. Smallpox vaccination and myopericarditis: a clinical review. J. Am. Coll. Cardiol. 2004;43:1503-1510.

    Not in our library10.1016/j.jacc.2003.11.053

  415. 415.

    Halsell JS, et al. Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel. JAMA. 2003;289:3283-3289.

    Not in our library10.1001/jama.289.24.3283

  416. 416.

    Bray M, Wright ME. Progressive vaccinia. Clin. Infect. Dis. 2003;36:766-774.

    Not in our library10.1086/374244

  417. 417.

    Decker MD, et al. Enhanced safety surveillance study of ACAM2000 smallpox vaccine among US military service members. Vaccine. 2021;39:5541-5547.

    Not in our library10.1016/j.vaccine.2021.08.041

  418. 418.

    Faix DJ, et al. Prospective safety surveillance study of ACAM2000 smallpox vaccine in deploying military personnel. Vaccine. 2020;38:7323-7330.

    Not in our library10.1016/j.vaccine.2020.09.037

  419. 419.

    Freeman R, Lenz B. Cutaneous reactions associated with ACAM2000 smallpox vaccination in a deploying U.S. Army unit. Mil. Med. 2015;180:e152-156.

    Not in our library10.7205/milmed-d-14-00218

  420. 420.

    McNeil MM, et al. Ischemic cardiac events and other adverse events following ACAM2000((R)) smallpox vaccine in the Vaccine Adverse Event Reporting System. Vaccine. 2014;32:4758-4765.

    Not in our library10.1016/j.vaccine.2014.06.034

  421. 421.

    Beachkofsky TM, et al. Adverse events following smallpox vaccination with ACAM2000 in a military population. Arch. Dermatol. 2010;146:656-661.

    Not in our library10.1001/archdermatol.2010.46

  422. 422.

    CDC. Monkeypox. https://www.cdc.gov/poxvirus/monkeypox/vaccines.html (2022).

    Not in our library

  423. 423.

    FDA. FDA approves first live, non-replicating vaccine to prevent smallpox and monkeypox. https://www.fda.gov/news-events/press-announcements/fda-approves-first-live-non-replicating-vaccine-prevent-smallpox-and-monkeypox (2019).

    Not in our library

  424. 424.

    Frey SE, et al. Safety and immunogenicity of IMVAMUNE(R) smallpox vaccine using different strategies for a post event scenario. Vaccine. 2013;31:3025-3033.

    Not in our library10.1016/j.vaccine.2013.04.050

  425. 425.

    Walsh SR, et al. Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized, controlled trial. J. Infect. Dis. 2013;207:1888-1897.

    Not in our library10.1093/infdis/jit105

  426. 426.

    von Sonnenburg F, et al. Safety and immunogenicity of modified vaccinia Ankara as a smallpox vaccine in people with atopic dermatitis. Vaccine. 2014;32:5696-5702.

    Not in our library10.1016/j.vaccine.2014.08.022

  427. 427.

    Overton ET, et al. Safety and immunogenicity of modified vaccinia Ankara-Bavarian Nordic smallpox vaccine in vaccinia-naive and experienced human immunodeficiency virus-infected individuals: an open-label, controlled clinical phase II trial. Open Forum Infect. Dis. 2015;2:ofv040.

    Not in our library10.1093/ofid/ofv040

  428. 428.

    Greenberg RN, et al. Safety, immunogenicity, and surrogate markers of clinical efficacy for modified vaccinia Ankara as a smallpox vaccine in HIV-infected subjects. J. Infect. Dis. 2013;207:749-758.

    Not in our library10.1093/infdis/jis753

  429. 429.

    Jones T. IMVAMUNE, an attenuated modified vaccinia Ankara virus vaccine for smallpox infection. Curr. Opin. Mol. Ther. 2008;10:407-417.

    Not in our library

  430. 430.

    Davies DH, et al. Antibody profiling by proteome microarray reveals the immunogenicity of the attenuated smallpox vaccine modified vaccinia virus ankara is comparable to that of Dryvax. J. Virol. 2008;82:652-663.

    Not in our library10.1128/jvi.01706-07

  431. 431.

    Phelps AL, et al. Comparative efficacy of modified vaccinia Ankara (MVA) as a potential replacement smallpox vaccine. Vaccine. 2007;25:34-42.

    Not in our library10.1016/j.vaccine.2006.07.022

  432. 432.

    Cosma A, et al. Evaluation of modified vaccinia virus Ankara as an alternative vaccine against smallpox in chronically HIV type 1-infected individuals undergoing HAART. AIDS Res. Hum. Retroviruses. 2007;23:782-793.

    Not in our library10.1089/aid.2006.0226

  433. 433.

    Meseda CA, et al. Enhanced immunogenicity and protective effect conferred by vaccination with combinations of modified vaccinia virus Ankara and licensed smallpox vaccine Dryvax in a mouse model. Virology. 2005;339:164-175.

    Not in our library10.1016/j.virol.2005.06.002

  434. 434.

    von Krempelhuber A, et al. A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE. Vaccine. 2010;28:1209-1216.

    Not in our library10.1016/j.vaccine.2009.11.030

  435. 435.

    Frey SE, et al. Clinical and immunologic responses to multiple doses of IMVAMUNE (Modified Vaccinia Ankara) followed by Dryvax challenge. Vaccine. 2007;25:8562-8573.

    Not in our library10.1016/j.vaccine.2007.10.017

  436. 436.

    Vollmar J, et al. Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine. Vaccine. 2006;24:2065-2070.

    Not in our library10.1016/j.vaccine.2005.11.022

  437. 437.

    Bavarian-Nordic.com. Bavarian Nordic announces US FDA approval of Jynneos s (smallpox and monkeypox vaccine, live; non-replicating) for prevention of smallpox and monkeypox disease in adults. https://www.bavarian-nordic.com/investor/news/news.aspx?news=5758 (2019).

    Not in our library

  438. 438.

    Earl PL, et al. Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus. Proc. Natl Acad. Sci. USA. 2008;105:10889-10894.

    Not in our library10.1073/pnas.0804985105

  439. 439.

    Keckler MS, et al. Establishment of the black-tailed prairie dog (Cynomys ludovicianus) as a novel animal model for comparing smallpox vaccines administered preexposure in both high- and low-dose monkeypox virus challenges. J. Virol. 2011;85:7683-7698.

    Not in our library10.1128/jvi.02174-10

  440. 440.

    Stittelaar KJ, et al. Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus. J. Virol. 2005;79:7845-7851.

    Not in our library10.1128/jvi.79.12.7845-7851.2005

  441. 441.

    Earl PL, et al. Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox. Nature. 2004;428:182-185.

    Not in our library10.1038/nature02331

  442. 442.

    Nigam P, et al. DNA/MVA HIV-1/AIDS vaccine elicits long-lived vaccinia virus-specific immunity and confers protection against a lethal monkeypox challenge. Virology. 2007;366:73-83.

    Not in our library10.1016/j.virol.2007.04.010

  443. 443.

    Petersen BW, et al. Vaccinating against monkeypox in the Democratic Republic of the Congo. Antivir. Res. 2019;162:171-177.

    Not in our library10.1016/j.antiviral.2018.11.004

  444. 444.

    Nguyen, L. B. L. et al. A prospective national cohort evaluating ring MVA vaccination as post-exposure prophylaxis for monkeypox. Nat. Med. 10.1038/d41591-022-00077-1 (2022).

    Not in our library10.1038/d41591-022-00077-1

  445. 445.

    Pittman PR, et al. Phase 3 efficacy trial of modified vaccinia Ankara as a vaccine against smallpox. N. Engl. J. Med. 2019;381:1897-1908.

    Not in our library10.1056/nejmoa1817307

  446. 446.

    de Nicolas-Ruanes B, et al. Monkeypox virus case with maculopapular exanthem and proctitis during the Spanish outbreak in 2022. J. Eur. Acad. Dermatol. Venereol. 2022;36:e658-e660.

    Not in our library10.1111/jdv.18300

  447. 447.

    WHO. Vaccines and immunization for monkeypox: Interim guidance, 14 June 2022. https://www.who.int/publications/i/item/who-mpx-immunization-2022.1 (2022).

    Not in our library

  448. 448.

    EMA. EMA recommends approval of Imvanex for the prevention of monkeypox disease. https://www.ema.europa.eu/en/news/ema-recommends-approval-imvanex-prevention-monkeypox-disease

    Not in our library

  449. 449.

    GlobeNewswire. Health Canada extends approval of IMVAMUNE to immunization against monkeypox and orthopox viruses. https://www.globenewswire.com/news-release/2020/11/12/2125193/0/en/Health-Canada-Extends-Approval-of-IMVAMUNE-to-Immunization-against-Monkeypox-and-Orthopox-Viruses.html (2020).

    Not in our library

  450. 450.

    GlobeNewswire. Bavarian Nordic expands capacity with U.S. contract manufacturer for filling of smallpox/monkeypox vaccines. https://www.globenewswire.com/en/news-release/2022/08/18/2501182/0/en/Bavarian-Nordic-Expands-Capacity-with-U-S-Contract-Manufacturer-for-Filling-of-Smallpox-Monkeypox-Vaccines.html (2022).

    Not in our library

  451. 451.

    FDA. Monkeypox update: FDA authorizes emergency use of JYNNEOS vaccine to increase vaccine supply. https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supply (2022).

    Not in our library

  452. 452.

    Frey SE, et al. Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naive subjects. Vaccine. 2015;33:5225-5234.

    Not in our library10.1016/j.vaccine.2015.06.075

  453. 453.

    Takahashi-Nishimaki F, et al. Genetic analysis of vaccinia virus Lister strain and its attenuated mutant LC16m8: production of intermediate variants by homologous recombination. J. Gen. Virol. 1987;68:2705-2710.

    Not in our library10.1099/0022-1317-68-10-2705

  454. 454.

    Morikawa S, et al. An attenuated LC16m8 smallpox vaccine: analysis of full-genome sequence and induction of immune protection. J. Virol. 2005;79:11873-11891.

    Not in our library10.1128/jvi.79.18.11873-11891.2005

  455. 455.

    Yoshikawa T, et al. Construction and characterization of bacterial artificial chromosomes harboring the full-length genome of a highly attenuated vaccinia virus LC16m8. PLoS ONE. 2018;13:e0192725.

    Not in our library10.1371/journal.pone.0192725

  456. 456.

    Omura N, et al. A novel system for constructing a recombinant highly-attenuated vaccinia virus strain (LC16m8) expressing foreign genes and its application for the generation of LC16m8-based vaccines against herpes simplex virus 2. Jpn J. Infect. Dis. 2018;71:229-233.

    Not in our library10.7883/yoken.jjid.2017.458

  457. 457.

    Yokote H, et al. Safety of attenuated smallpox vaccine LC16m8 in immunodeficient mice. Clin. Vaccin. Immunol. 2014;21:1261-1266.

    Not in our library10.1128/cvi.00199-14

  458. 458.

    Meseda CA, et al. Comparative evaluation of the immune responses and protection engendered by LC16m8 and Dryvax smallpox vaccines in a mouse model. Clin. Vaccin. Immunol. 2009;16:1261-1271.

    Not in our library10.1128/cvi.00040-09

  459. 459.

    Empig C, et al. Highly attenuated smallpox vaccine protects rabbits and mice against pathogenic orthopoxvirus challenge. Vaccine. 2006;24:3686-3694.

    Not in our library10.1016/j.vaccine.2005.03.029

  460. 460.

    Kidokoro M, Tashiro M, Shida H. Genetically stable and fully effective smallpox vaccine strain constructed from highly attenuated vaccinia LC16m8. Proc. Natl Acad. Sci. USA. 2005;102:4152-4157.

    Not in our library10.1073/pnas.0406671102

  461. 461.

    Yokote H, et al. Vaccinia virus strain LC16m8 defective in the B5R gene keeps strong protection comparable to its parental strain Lister in immunodeficient mice. Vaccine. 2015;33:6112-6119.

    Not in our library10.1016/j.vaccine.2015.07.076

  462. 462.

    Saijo M, et al. LC16m8, a highly attenuated vaccinia virus vaccine lacking expression of the membrane protein B5R, protects monkeys from monkeypox. J. Virol. 2006;80:5179-5188.

    Not in our library10.1128/jvi.02642-05

  463. 463.

    Gordon SN, et al. Smallpox vaccine safety is dependent on T cells and not B cells. J. Infect. Dis. 2011;203:1043-1053.

    Not in our library10.1093/infdis/jiq162

  464. 464.

    Iizuka I, et al. A single vaccination of nonhuman primates with highly attenuated smallpox vaccine, LC16m8, provides long-term protection against monkeypox. Jpn J. Infect. Dis. 2017;70:408-415.

    Not in our library10.7883/yoken.jjid.2016.417

  465. 465.

    Kennedy JS, et al. Safety and immunogenicity of LC16m8, an attenuated smallpox vaccine in vaccinia-naive adults. J. Infect. Dis. 2011;204:1395-1402.

    Not in our library10.1093/infdis/jir527

  466. 466.

    Saito T, et al. Clinical and immunological response to attenuated tissue-cultured smallpox vaccine LC16m8. JAMA. 2009;301:1025-1033.

    Not in our library10.1001/jama.2009.289

  467. 467.

    Kenner J, et al. LC16m8: an attenuated smallpox vaccine. Vaccine. 2006;24:7009-7022.

    Not in our library10.1016/j.vaccine.2006.03.087

  468. 468.

    Nishiyama Y, et al. Freeze-dried live attenuated smallpox vaccine prepared in cell culture “LC16-KAKETSUKEN”: post-marketing surveillance study on safety and efficacy compliant with good clinical practice. Vaccine. 2015;33:6120-6127.

    Not in our library10.1016/j.vaccine.2015.09.067

  469. 469.

    Eto A, et al. Recent advances in the study of live attenuated cell-cultured smallpox vaccine LC16m8. Vaccine. 2015;33:6106-6111.

    Not in our library10.1016/j.vaccine.2015.07.111

  470. 470.

    Eto A, et al. Profiling of the antibody response to attenuated LC16m8 smallpox vaccine using protein array analysis. Vaccine. 2019;37:6588-6593.

    Not in our library10.1016/j.vaccine.2019.09.006

  471. 471.

    Friedman D. Safety and immunogenicity of LC16m8, an attenuated smallpox vaccine in vaccinia-naive adults. J. Infect. Dis. 2012;206:1149-1150.

    Not in our library10.1093/infdis/jis453

  472. 472.

    Johnson BF, et al. Serological responses in humans to the smallpox vaccine LC16m8. J. Gen. Virol. 2011;92:2405-2410.

    Not in our library10.1099/vir.0.034207-0

  473. 473.

    Healthworld.com. Japan approves smallpox vaccine to prevent monkeypox. https://health.economictimes.indiatimes.com/news/industry/japan-approves-smallpox-vaccine-to-prevent-monkeypox/93321404 (2022).

    Not in our library

  474. 474.
    The 2017 human monkeypox outbreak in Nigeria—Report of outbreak experience and response in the Niger Delta University Teaching Hospital, Bayelsa State, Nigeria · 2019
    No notice
  475. 475.

    Ogoina D, et al. Clinical course and outcome of human monkeypox in Nigeria. Clin. Infect. Dis. 2020;71:e210-e214.

    Not in our library10.1093/cid/ciaa143

  476. 476.

    ABC NEWS. Moderna considering creating an mRNA monkeypox vaccine amid growing demand for shots. https://abcnews.go.com/Health/moderna-creating-mrna-monkeypox-vaccine-amid-growing-demand/story?id=87875414 (2022).

    Not in our library

  477. 477.

    Tonix Pharmaceuticals, TNX-801. https://www.tonixpharma.com/tnx-801/ (2022).

    Not in our library

  478. 478.
    Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments · 2018
    No notice
  479. 479.

    Noyce, R et al. Synthetic chimeric horsepox virus (scHPXV) vaccination protects macaques from monkeypox. https://www.tonixpharma.com/wp-content/uploads/2021/11/Synthetic-Chimeric-Horsepox-Virus-scHPXV-Vaccination-Protects-Macaques-from-Monkeypox.pdf (2020).

    Not in our library10.3390/v15020356

  480. 480.

    Gao, A. & Gao. S. In silico identification of non-cross-reactive epitopes for monkeypox cell surface-binding protein. Preprint at Research Square10.21203/rs.3.rs-1693979/v1 (2022).

    Not in our library

  481. 481.

    Peng C, Moss B. Repair of a previously uncharacterized second host-range gene contributes to full replication of modified vaccinia virus Ankara (MVA) in human cells. Proc. Natl Acad. Sci. USA. 2020;117:3759-3767.

    Not in our library10.1073/pnas.1921098117

  482. 482.

    Edghill-Smith Y, et al. Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge. J. Infect. Dis. 2005;191:372-381.

    Not in our library10.1086/427265

  483. 483.

    Hutson CL, et al. Monkeypox zoonotic associations: insights from laboratory evaluation of animals associated with the multi-state US outbreak. Am. J. Trop. Med. Hyg. 2007;76:757-768.

    Not in our library10.4269/ajtmh.2007.76.757

  484. 484.

    Marennikova SS, Seluhina EM. Susceptibility of some rodent species to monkeypox virus, and course of the infection. Bull. World Health Organ. 1976;53:13-20.

    Not in our library

  485. 485.

    Arita I, Henderson DA. Smallpox and monkeypox in non-human primates. Bull. World Health Organ. 1968;39:277-283.

    Not in our library

  486. 486.

    Shelukhina, E. M., Shenkman, L. S., Rozina, E. E. & Marennikova, S. S. Possible mechanism of orthopoxvirus preservation in nature. Vopr. Virusol. 368–372 (1979).

    Not in our library

  487. 487.

    Earl PL, Americo JL, Cotter CA, Moss B. Comparative live bioluminescence imaging of monkeypox virus dissemination in a wild-derived inbred mouse (Mus musculus castaneus) and outbred African dormouse (Graphiurus kelleni). Virology. 2015;475:150-158.

    Not in our library10.1016/j.virol.2014.11.015

  488. 488.

    Americo JL, Moss B, Earl PL. Identification of wild-derived inbred mouse strains highly susceptible to monkeypox virus infection for use as small animal models. J. Virol. 2010;84:8172-8180.

    Not in our library10.1128/jvi.00621-10

  489. 489.

    Earl PL, Americo JL, Moss B. Genetic studies of the susceptibility of classical and wild-derived inbred mouse strains to monkeypox virus. Virology. 2015;481:161-165.

    Not in our library10.1016/j.virol.2015.02.048

  490. 490.

    Jezek Z, Fenner F. Human monkeypox. Monogr. Virol. 1988;17:1-140.

    Not in our library10.1159/000416456

  491. 491.

    Reynolds MG, Carroll DS, Karem KL. Factors affecting the likelihood of monkeypox’s emergence and spread in the post-smallpox era. Curr. Opin. Virol. 2012;2:335-343.

    Not in our library10.1016/j.coviro.2012.02.004

  492. 492.

    Falendysz EA, et al. Further assessment of monkeypox virus infection in gambian pouched rats (Cricetomys gambianus) using in vivo bioluminescent imaging. PLoS Negl. Trop. Dis. 2015;9:e0004130.

    Not in our library10.1371/journal.pntd.0004130

  493. 493.

    Falendysz EA, et al. Evaluation of monkeypox virus infection of black-tailed prairie dogs (Cynomys ludovicianus) using in vivo bioluminescent imaging. J. Wildl. Dis. 2014;50:524-536.

    Not in our library10.7589/2013-07-171

  494. 494.

    Marennikova SS, Shelukhina EM, Zhukova OA. Experimental infection of squirrels Sciurus vulgaris by monkey pox virus. Acta Virol. 1989;33:399.

    Not in our library

  495. 495.

    Sergeev AA, et al. Using the ground squirrel (Marmota bobak) as an animal model to assess monkeypox drug efficacy. Transbound. Emerg. Dis. 2017;64:226-236.

    Not in our library10.1111/tbed.12364

  496. 496.

    Sbrana E, Xiao SY, Newman PC, Tesh RB. Comparative pathology of North American and central African strains of monkeypox virus in a ground squirrel model of the disease. Am. J. Trop. Med Hyg. 2007;76:155-164.

    Not in our library10.4269/ajtmh.2007.76.155

  497. 497.
    A Silent Enzootic of an Orthopoxvirus in Ghana, West Africa: Evidence for Multi-Species Involvement in the Absence of Widespread Human Disease · 2010
    No notice
  498. 498.

    Khodakevich L, et al. Monkeypox virus in relation to the ecological features surrounding human settlements in Bumba zone, Zaire. Trop. Geogr. Med. 1987;39:56-63.

    Not in our library

  499. 499.

    Gispen R, Brand-Saathof BB, Hekker AC. Monkeypox-specific antibodies in human and simian sera from the Ivory Coast and Nigeria. Bull. World Health Organ. 1976;53:355-360.

    Not in our library

  500. 500.

    Mucker EM, et al. Susceptibility of marmosets (Callithrix jacchus) to monkeypox virus: a low dose prospective model for monkeypox and smallpox disease. PLoS ONE. 2015;10:e0131742.

    Not in our library10.1371/journal.pone.0131742

  501. 501.

    Breman JG, et al. Human poxvirus disease after smallpox eradication. Am. J. Trop. Med. Hyg. 1977;26:273-281.

    Not in our library10.4269/ajtmh.1977.26.273

  502. 502.

    Arita I, et al. Outbreaks of monkeypox and serological surveys in nonhuman primates. Bull. World Health Organ. 1972;46:625-631.

    Not in our library

  503. 503.

    Sauer RM, et al. Studies on a pox disease of monkeys. I. Pathology. Am. J. Vet. Res. 1960;21:377-380.

    Not in our library

  504. 504.

    Breman JG, Bernadou J, Nakano JH. Poxvirus in West African nonhuman primates: serological survey results. Bull. World Health Organ. 1977;55:605-612.

    Not in our library

  505. 505.

    Peters JC. An epizootic of monkey pox at Rotterdam zoo. Int. Zoo. Yearb. 1966;6:274-275.

    Not in our library10.1111/j.1748-1090.1966.tb01794.x

  506. 506.

    Elizaga ML, et al. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review. PLoS ONE. 2013;8:e54407.

    Not in our library10.1371/journal.pone.0054407

  507. 507.

    Overton ET, et al. A randomized phase II trial to compare safety and immunogenicity of the MVA-BN smallpox vaccine at various doses in adults with a history of AIDS. Vaccine. 2020;38:2600-2607.

    Not in our library10.1016/j.vaccine.2020.01.058

  508. 508.

    Greenberg RN, et al. A randomized, double-blind, placebo-controlled phase II trial investigating the safety and immunogenicity of modified vaccinia ankara smallpox vaccine (MVA-BN(R)) in 56-80-year-old subjects. PLoS ONE. 2016;11:e0157335.

    Not in our library10.1371/journal.pone.0157335

  509. 509.
    Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial. · 2018
    Not checked
  510. 510.

    Zitzmann-Roth EM, et al. Cardiac safety of modified vaccinia Ankara for vaccination against smallpox in a young, healthy study population. PLoS ONE. 2015;10:e0122653.

    Not in our library10.1371/journal.pone.0122653

  511. 511.

    Seaman MS, et al. Effect of vaccination with modified vaccinia Ankara (ACAM3000) on subsequent challenge with Dryvax. J. Infect. Dis. 2010;201:1353-1360.

    Not in our library10.1086/651560

  512. 512.

    Wilck MB, et al. Safety and immunogenicity of modified vaccinia Ankara (ACAM3000): effect of dose and route of administration. J. Infect. Dis. 2010;201:1361-1370.

    Not in our library10.1086/651561

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    Jang HC, et al. A randomized, double-blind, controlled clinical trial to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy volunteers. Vaccine. 2010;28:5845-5849.

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