4.7 Review

Potential SARS-CoV-2 main protease inhibitors

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DRUG DISCOVERY TODAY
卷 26, 期 3, 页码 804-816

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ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2020.12.005

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  1. NIH [R15 CA213185-01A1]
  2. Division of Intramural Research of the National Institute of Environmental Health Sciences/NIH [Z01-ES043010]

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This review focuses on recent developments in the search for small-molecule inhibitors targeting the SARS-CoV-2 M-pro, aiming at discovering and designing drugs targeting the key target in the viral replication cycle.
The coronavirus disease 2019 (COVID-19) pandemic has prompted an urgent need for new treatment strategies. No target-specific drugs are currently available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but new drug candidates targeting the viral replication cycle are being explored. A prime target of drug-discovery efforts is the SARS-CoV-2 main protease (M-pro). The main proteases of different coronaviruses, including SARS-CoV-2, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), share a structurally conserved substrate-binding region that can be exploited to design new protease inhibitors. With the recent reporting of the X-ray crystal structure of the SARS-CoV-2 Mpro, studies to discover M-pro inhibitors using both virtual and in vitro screening are progressing rapidly. This review focusses on the recent developments in the search for small-molecule inhibitors targeting the SARS-CoV-2 M-pro.

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