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SARS-CoV-2 M pro inhibitors with antiviral activity in a transgenic mouse model
Jingxin Qiao, Yue-Shan Li, Rui Zeng and 40 more
Science · 2021 · CC BY
Abstract
Targeting the SARS-CoV-2 main protease Vaccines are an important tool in the fight against COVID-19, but developing antiviral drugs is also a high priority, especially with the rise of variants that may partially evade vaccines. The viral protein main protease is required for cleaving precursor polyproteins into functional viral proteins. This essential function makes it a key drug target. Qiao et al. designed 32 inhibitors based on either boceprevir or telaprevir, both of which are protease inhibitors approved to treat hepatitis C virus. Six compounds protected cells from viral infection with high potency, and two of these were selected for in vivo studies based on pharmokinetic experiments. Both showed strong antiviral activity in a mouse model. Science , this issue p. 1374
References 41
- 1.
- 2.
- 3.
- 4.
P. Smith, Covid-19 in Australia: Most infected health workers in Victoria’s second wave acquired virus at work. BMJ 370, m3350 (2020 ).
Not in our library10.1136/bmj.m3350
- 5.
M.-K. Looi, Covid-19: Is a second wave hitting Europe? BMJ 371, m4113 (2020 ).
Not in our library10.1136/bmj.m4113
- 6.
Y. Chen, Q. Liu, D. Guo, Emerging coronaviruses: Genome structure, replication, and pathogenesis. J. Med. Virol. 92, 418–423 (2020 ).
Not in our library10.1002/jmv.25681
- 7.
R. Hilgenfeld, From SARS to MERS: Crystallographic studies on coronaviral proteases enable antiviral drug design. FEBS J. 281, 4085–4096 (2014 ).
Not in our library10.1111/febs.12936
- 8.
K. Anand, J. Ziebuhr, P. Wadhwani, J. R. Mesters, R. Hilgenfeld, Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs. Science 300, 1763–1767 (2003 ).
Not in our library10.1126/science.1085658
- 9.
L. Zhang, D. Lin, Y. Kusov, Y. Nian, Q. Ma, J. Wang, A. von Brunn, P. Leyssen, K. Lanko, J. Neyts, A. de Wilde, E. J. Snijder, H. Liu, R. Hilgenfeld, α-Ketoamides as broad-spectrum inhibitors of coronavirus and enterovirus replication: Structure-based design, synthesis, and activity assessment. J. Med. Chem. 63, 4562–4578 (2020 ).
Not in our library10.1021/acs.jmedchem.9b01828
- 10.
T. Pillaiyar, M. Manickam, V. Namasivayam, Y. Hayashi, S.-H. Jung, An overview of severe acute respiratory syndrome–coronavirus (SARS-CoV) 3CL protease inhibitors: Peptidomimetics and small molecule chemotherapy. J. Med. Chem. 59, 6595–6628 (2016 ).
Not in our library10.1021/acs.jmedchem.5b01461
- 11.
Z. Jin, X. Du, Y. Xu, Y. Deng, M. Liu, Y. Zhao, B. Zhang, X. Li, L. Zhang, C. Peng, Y. Duan, J. Yu, L. Wang, K. Yang, F. Liu, R. Jiang, X. Yang, T. You, X. Liu, X. Yang, F. Bai, H. Liu, X. Liu, L. W. Guddat, W. Xu, G. Xiao, C. Qin, Z. Shi, H. Jiang, Z. Rao, H. Yang, Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 582, 289–293 (2020 ).
Not in our library10.1038/s41586-020-2223-y
- 12.
- 13.
- 14.
R. L. Hoffman, R. S. Kania, M. A. Brothers, J. F. Davies, R. A. Ferre, K. S. Gajiwala, M. He, R. J. Hogan, K. Kozminski, L. Y. Li, J. W. Lockner, J. Lou, M. T. Marra, L. J. Mitchell Jr.., B. W. Murray, J. A. Nieman, S. Noell, S. P. Planken, T. Rowe, K. Ryan, G. J. Smith 3rd, J. E. Solowiej, C. M. Steppan, B. Taggart, Discovery of ketone-based covalent inhibitors of coronavirus 3CL proteases for the potential therapeutic treatment of COVID-19. J. Med. Chem. 63, 12725–12747 (2020 ).
Not in our library10.1021/acs.jmedchem.0c01063
- 15.
B. Boras et al., Discovery of a Novel Inhibitor of Coronavirus 3CL Protease as a Clinical Candidate for the Potential Treatment of COVID-19. bioRxiv [preprint]. 13 September 2020.293498
Not in our library
- 16.
M. Westberg et al., Rational design of a new class of protease inhibitors for the potential treatment of coronavirus diseases. bioRxiv [preprint]. 16 September 2020.275891
Not in our library
- 17.
C. Ma, M. D. Sacco, B. Hurst, J. A. Townsend, Y. Hu, T. Szeto, X. Zhang, B. Tarbet, M. T. Marty, Y. Chen, J. Wang, Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Res. 30, 678–692 (2020 ).
Not in our library10.1038/s41422-020-0356-z
- 18.
M. D. Sacco, C. Ma, P. Lagarias, A. Gao, J. A. Townsend, X. Meng, P. Dube, X. Zhang, Y. Hu, N. Kitamura, B. Hurst, B. Tarbet, M. T. Marty, A. Kolocouris, Y. Xiang, Y. Chen, J. Wang, Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against Mpro and cathepsin L. Sci. Adv. 6, eabe0751 (2020 ).
Not in our library10.1126/sciadv.abe0751
- 19.
W. Zhu, M. Xu, C. Z. Chen, H. Guo, M. Shen, X. Hu, P. Shinn, C. Klumpp-Thomas, S. G. Michael, W. Zheng, Identification of SARS-CoV-2 3CL protease inhibitors by a quantitative high-throughput screening. ACS Pharmacol. Transl. Sci. 3, 1008–1016 (2020 ).
Not in our library10.1021/acsptsci.0c00108
- 20.
K. S. Yang, X. R. Ma, Y. Ma, Y. R. Alugubelli, D. A. Scott, E. C. Vatansever, A. K. Drelich, B. Sankaran, Z. Z. Geng, L. R. Blankenship, H. E. Ward, Y. J. Sheng, J. C. Hsu, K. C. Kratch, B. Zhao, H. S. Hayatshahi, J. Liu, P. Li, C. A. Fierke, C. K. Tseng, S. Xu, W. R. Liu, A quick route to multiple highly potent SARS-CoV-2 main protease inhibitors. ChemMedChem 15, 1–8 (2020 ).
Not in our library10.1002/cmdc.202000924
- 21.
- 22.
R. Cannalire, C. Cerchia, A. R. Beccari, F. S. Di Leva, V. Summa, Targeting SARS-CoV-2 proteases and polymerase for COVID-19 treatment: State of the art and future opportunities. J. Med. Chem. acs.jmedchem.0c01140 (2020 ).
Not in our library10.1021/acs.jmedchem.0c01140
- 23.
C. Gampe, V. A. Verma, Curse or cure? A perspective on the developability of aldehydes as active pharmaceutical ingredients. J. Med. Chem. 63, 14357–14381 (2020 ).
Not in our library10.1021/acs.jmedchem.0c01177
- 24.
P. S. Dragovich, T. J. Prins, R. Zhou, S. E. Webber, J. T. Marakovits, S. A. Fuhrman, A. K. Patick, D. A. Matthews, C. A. Lee, C. E. Ford, B. J. Burke, P. A. Rejto, T. F. Hendrickson, T. Tuntland, E. L. Brown, J. W. Meador 3rd, R. A. Ferre, J. E. V. Harr, M. B. Kosa, S. T. Worland, Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 4. Incorporation of P1 lactam moieties as L-glutamine replacements. J. Med. Chem. 42, 1213–1224 (1999 ).
Not in our library10.1021/jm9805384
- 25.
R. P. Jain, H. I. Pettersson, J. Zhang, K. D. Aull, P. D. Fortin, C. Huitema, L. D. Eltis, J. C. Parrish, M. N. G. James, D. S. Wishart, J. C. Vederas, Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of severe acute respiratory syndrome 3CLpro. J. Med. Chem. 47, 6113–6116 (2004 ).
Not in our library10.1021/jm0494873
- 26.
Y. Yip, F. Victor, J. Lamar, R. Johnson, Q. M. Wang, D. Barket, J. Glass, L. Jin, L. Liu, D. Venable, M. Wakulchik, C. Xie, B. Heinz, E. Villarreal, J. Colacino, N. Yumibe, M. Tebbe, J. Munroe, S.-H. Chen, Discovery of a novel bicycloproline P2 bearing peptidyl α-ketoamide LY514962 as HCV protease inhibitor. Bioorg. Med. Chem. Lett. 14, 251–256 (2004 ).
Not in our library10.1016/j.bmcl.2003.09.074
- 27.
H. K. Ganguly, G. Basu, Conformational landscape of substituted prolines. Biophys. Rev. 12, 25–39 (2020 ).
Not in our library10.1007/s12551-020-00621-8
- 28.
P. Bazzini, C. G. Wermuth, in The Practice of Medicinal Chemistry, C. G. Wermuth, D. Aldous, P. Raboisson, D. Rognan, Eds. (Academic Press, ed. 4, 2015), pp. 319–357.
Not in our library
- 29.
Y. C. Martin, A bioavailability score. J. Med. Chem. 48, 3164–3170 (2005 ).
Not in our library10.1021/jm0492002
- 30.
S.-H. Sun, Q. Chen, H.-J. Gu, G. Yang, Y.-X. Wang, X.-Y. Huang, S.-S. Liu, N.-N. Zhang, X.-F. Li, R. Xiong, Y. Guo, Y.-Q. Deng, W.-J. Huang, Q. Liu, Q.-M. Liu, Y.-L. Shen, Y. Zhou, X. Yang, T.-Y. Zhao, C.-F. Fan, Y.-S. Zhou, C.-F. Qin, Y.-C. Wang, A mouse model of SARS-CoV-2 infection and pathogenesis. Cell Host Microbe 28, 124–133.e4 (2020 ).
Not in our library10.1016/j.chom.2020.05.020
- 31.
M. S. Weiss, R. Hilgenfeld, On the use of the merging R factor as a quality indicator for X-ray data. J. Appl. Crystallogr. 30, 203–205 (1997 ).
Not in our library10.1107/s0021889897003907
- 32.
P. A. Karplus, K. Diederichs, Linking crystallographic model and data quality. Science 336, 1030–1033 (2012 ).
Not in our library10.1126/science.1218231
- 33.
- 34.
- 35.
- 36.
A. Vagin, A. Teplyakov, Molecular replacement with MOLREP. Acta Crystallogr. D 66, 22–25 (2010 ).
Not in our library10.1107/s0907444909042589
- 37.
L. Zhu, S. George, M. F. Schmidt, S. I. Al-Gharabli, J. Rademann, R. Hilgenfeld, Peptide aldehyde inhibitors challenge the substrate specificity of the SARS-coronavirus main protease. Antiviral Res. 92, 204–212 (2011 ).
Not in our library10.1016/j.antiviral.2011.08.001
- 38.
- 39.
O. Kovalevskiy, R. A. Nicholls, F. Long, A. Carlon, G. N. Murshudov, Overview of refinement procedures within REFMAC5: Utilizing data from different sources. Acta Crystallogr. D 74, 215–227 (2018 ).
Not in our library10.1107/s2059798318000979
- 40.
G. Bricogne et al., BUSTER version 2.10.3 (Global Phasing Ltd., 2017).
Not in our library
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