Research Article

Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease

See allHide authors and affiliations

Science  22 Apr 2020:
eabb4489
DOI: 10.1126/science.abb4489

Abstract

SARS-CoV-2 is the etiological agent responsible for the global COVID-19 outbreak. The main protease (Mpro) of SARS-CoV-2 is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro. Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The X-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a or 11b, both determined at 1.5 Å resolution, showed that the aldehyde groups of 11a and 11b are covalently bound to Cys145 of Mpro. Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity, suggesting that these compounds are promising drug candidates.

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

View Full Text

Stay Connected to Science