SARS-CoV-2 M pro inhibitors with antiviral activity in a transgenic mouse model
Open accessAbstract
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
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Covalent inhibitor discovery against SARS-CoV-2 Mpro emerged from work on SARS-CoV-1 protease inhibitors.
“The discovery of covalent inhibitors against SARS-CoV-2 Mpro emerged from extensive work on protease inhibitors for SARS-CoV-1, which is the causative virus for severe acute respiratory syndrome coronavirus 1 (SARS1)100.”
From Advances in covalent drug discovery (2022) · cites this paper as [100]
SARS-CoV-2 replication depends on Mpro cleavage of pp1a and pp1ab into functional viral proteins.
“Viral replication depends on successful cleavage of pp1a and pp1ab by the Mpro (also referred to as 3CLpro), which is a cysteine protease, into functional viral proteins100.”
From Advances in covalent drug discovery (2022) · cites this paper as [100]
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Self-citation
- Authors
- Qiao, J., Li, Y.-S., Zeng, R., Liu, F.-L., Luo, R.-H., Huang, C., Wang, Y.-F., Zhang, J., Quan, B., Shen, C., Mao, X., Liu, X., Sun, W., Yang, W., Ni, X., Wang, K., Xu, L., Duan, Z.-L., Zou, Q.-C., Zhang, H.-L., Qu, W., Long, Y.-H.-P., Li, M.-H., Yang, R.-C., Liu, X., You, J., Zhou, Y., Yao, R., Li, W.-P., Liu, J.-M., Chen, P., Liu, Y., Lin, G.-F., Yang, X., Zou, J., Li, L., Hu, Y., Lu, G.-W., Li, W.-M., Wei, Y.-Q., Zheng, Y.-T., Lei, J., & Yang, S.
- Affiliations
- Sichuan University (CN)
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
- Kunming Institute of Zoology (CN)
- Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
- Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.
- Corresponding author
- Qiao, Jingxin
- Zeng, Rui
- Liu, Feng-Liang
- Luo, Rong-Hua
- Huang, Chong
- Zheng, Yong-Tang
- Lei, Jian
- Yang, Shengyong
- ORCID
- Qiao, Jingxin
- Li, Yue-Shan
- Zeng, Rui
- Liu, Feng-Liang
- Luo, Rong-Hua
- Huang, Chong
- Wang, Yi-Fei
- Zhang, Jie
- Quan, Baoxue
- Shen, Chenjian
- Mao, Xin
- Liu, Xinlei
- Sun, Weining
- Yang, Wei
- Ni, Xincheng
- Wang, Kai
- Xu, Ling
- Duan, Zi-Lei
- Zou, Qing-Cui
- Zhang, Hai-Lin
- Qu, Wang
- Long, Yang-Hao-Peng
- Li, Ming-Hua
- Yang, Rui-Cheng
- Liu, Xiaolong
- You, Jing
- Zhou, Yangli
- Yao, Rui
- Li, Wen-Pei
- Liu, Jing-Ming
- Chen, Pei
- Liu, Yang
- Lin, Gui-Feng
- Yang, Xin
- Zou, Jun
- Li, Linli
- Hu, Yiguo
- Lu, Guang-Wen
- Li, Wei-Min
- Wei, Yu-Quan
- Zheng, Yong-Tang
- Lei, Jian
- Yang, Shengyong
- Venue
- Science
- Published
- 2021-03-26
- Volume
- 371
- Issue
- 6536
- Pages
- 1374-1378
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8099175
- OpenAlex
- W3131767541
- Cited by
- 465
- References
- 40
- Citations by year
- 2026: 28 · 2025: 55 · 2024: 74 · 2023: 93 · 2022: 125 · 2021: 90
- FWCI
- 32.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron) (submittedVersion, cc-by)
- DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron)
- Funders
- Department of Science and Technology of Sichuan Province (2020YFS0006, 2020YFS0010)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, main protease, Mpro inhibitors, antiviral agents, COVID-19 pandemic, boceprevir, telaprevir, protease inhibitors, transgenic mouse model, pharmacokinetics, drug repurposing, hepatitis C virus
- MeSH terms
- COVID-19, Coronavirus 3C Proteases, COVID-19 Drug Treatment, Animals, Antiviral Agents, Cell Line, Cell Survival, Disease Models, Animal, Humans, Lung, Mice, Transgenic, Oligopeptides, Proline, Protease Inhibitors, Virus Replication, Drug Design, Interferon-beta, Rats, Sprague-Dawley, Viral Load, Mice, Rats, Chemokine CXCL10
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