Potential SARS-CoV-2 main protease inhibitors

Drug Discov Today. 2021 Mar;26(3):804-816. doi: 10.1016/j.drudis.2020.12.005. Epub 2020 Dec 9.


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 (Mpro). 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 Mpro 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 Mpro.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • COVID-19 Drug Treatment*
  • Coronavirus 3C Proteases* / antagonists & inhibitors
  • Coronavirus 3C Proteases* / chemistry
  • Coronavirus 3C Proteases* / metabolism
  • Drug Design
  • Drug Discovery / methods*
  • Humans
  • SARS-CoV-2* / drug effects
  • SARS-CoV-2* / physiology
  • Virus Replication / drug effects


  • Coronavirus 3C Proteases