Potential SARS-CoV-2 main protease inhibitors

• Published in: Drug discovery today 2021-03, Vol.26 (3), p.804-816
• Main Authors: Banerjee, Riddhidev, Perera, Lalith, Tillekeratne, L.M. Viranga
• Format: Article
• Language: English
• Subjects: Coronavirus 3C Proteases - antagonists & inhibitors; Coronavirus 3C Proteases - chemistry; Coronavirus 3C Proteases - metabolism; COVID-19 Drug Treatment; Drug Design; Drug Discovery - methods; Humans; Review; SARS-CoV-2 - drug effects; SARS-CoV-2 - physiology; Virus Replication - drug effects
• ISSN: 1359-6446; 1878-5832; 1878-5832
• DOI: 10.1016/j.drudis.2020.12.005

[Display omitted] •The SARS-CoV-2 main protease is a prime drug target.•Coronavirus main proteases share a structurally conserved substrate-binding region.•The structure and sequence similarity of SARS-CoV-2 to SARS-CoV readily allows testing of inhibitors designed for the latter.•Both covalent and non-covalent inhibitors of the SARS-CoV-2 main protease have been designed. 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.