Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)

Abstract

Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection.

Cited by papers we hold 10

• Targeting host cell proteases as a potential treatment strategy to limit the spread of SARS‐CoV‐2 in the respiratory tract · 2021
  Not checked
• Characterization of SARS-CoV-2 Variants N501Y.V1 and N501Y.V2 Spike on Viral Infectivity · 2021
  Not checked
• Therapeutic approaches against coronaviruses acute respiratory syndrome · 2021
  Not checked
• COVID-19 Therapeutic Options Under Investigation · 2020
  Not checked
• The role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors. · 2020
  Not checked
• Antimicrobial Resistance as a Hidden Menace Lurking Behind the COVID-19 Outbreak: The Global Impacts of Too Much Hygiene on AMR · 2020
  Not checked
• Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19 · 2020
  No notice
• Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes · 2020
  No notice
• Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics · 2020
  No notice
• From SARS to MERS, Thrusting Coronaviruses into the Spotlight · 2019
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.