Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir
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Abstract
A wrench in the works of COVID-19: Understanding the inner workings of the virus that causes coronavirus disease 2019 (COVID-19) may help us to disrupt it. Yin et al. focused on the viral polymerase essential for replicating viral RNA. They determined a structure of the polymerase bound to RNA and to the drug remdesivir. Remdesivir mimics an RNA nucleotide building block and is covalently linked to the replicating RNA, which blocks further synthesis of RNA. The structure provides a template for designing improved therapeutics against the viral polymerase. Science , this issue p. 1499
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SARS-CoV-2 catalytic virulence factors, such as its two proteases, Mpro and PLpro, and the RNA-dependent RNA polymerase (Rdrp), are potentially targetable by a PROTAC.
“but SARS-CoV-2 catalytic virulence factors, such as its two proteases, Mpro and PLpro201, and the RNA-dependent RNA polymerase (Rdrp), which is the target of remdesivir202, are potentially targetable by a PROTAC.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [202]
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- Authors
- Yin, W., Mao, C., Luan, X., Shen, D.-D., Shen, Q., Su, H., Wang, X., Zhou, F., Zhao, W., Gao, M., Chang, S., Xie, Y.-C., Tian, G., Jiang, H.-W., Tao, S.-C., Shen, J., Jiang, Y., Jiang, H., Xu, Y., Zhang, S., Zhang, Y., & Xu, H. E.
- Affiliations
- Chinese Academy of Sciences (CN)
- Sir Run Run Shaw Hospital (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Department of Biophysics, and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
- Biortus (China) (CN)
- The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Xu, Yechun
- Zhang, Shuyang
- Zhang, Yan
- Xu, H. Eric
- ORCID
- Venue
- Science
- Published
- 2020-06-26
- Volume
- 368
- Issue
- 6498
- Pages
- 1499-1504
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7199908
- OpenAlex
- W3022734398
- Cited by
- 1,219
- References
- 51
- Citations by year
- 2026: 54 · 2025: 80 · 2024: 91 · 2023: 154 · 2022: 214 · 2021: 352 · 2020: 274
- FWCI
- 32.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31770796)
- National Key Research and Development Program of China Stem Cell and Translational Research (2016YFA050230)
- National Science Foundation of China (81922071)
- National Science and Technology Major Project (2018ZX09711002)
- Shanghai Municipal Science and Technology Major Project (2019SHZDZX02)
- Jack Ma Foundation (2020-CMKYGG-05)
- CAMS Innovation Fund for "13th Five-Year" National Science and Technology Major Project (2019ZX09734001-002)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, RNA-dependent RNA polymerase, remdesivir, antiviral drug mechanism, viral RNA replication, chain termination, cryo-EM structure, drug design
- MeSH terms
- Betacoronavirus, SARS-CoV-2, Coronavirus RNA-Dependent RNA Polymerase, Adenosine Monophosphate, Alanine, Antiviral Agents, Enzyme Inhibitors, Models, Molecular, Protein Conformation, RNA-Dependent RNA Polymerase, RNA, Viral, Virus Replication, Viral Nonstructural Proteins, Catalytic Domain, Cryoelectron Microscopy, Multiprotein Complexes
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