Discovery of novel SARS-CoV-2 inhibitors targeting the main protease M^pro by virtual screenings and hit optimization.

ABSTRACT: Two years after its emergence, SARS-CoV-2 still represents a serious and global threat to human health. Antiviral drug development usually takes a long time and, to increase the chances of success, chemical variability of hit compounds represents a valuable source for the discovery of new antivirals. In this work, we applied a platform of variably oriented virtual screening campaigns to seek for novel chemical scaffolds for SARS-CoV-2 main protease (M^pro) inhibitors. The study on the resulting 30 best hits led to the identification of a series of structurally unrelated M^pro inhibitors. Some of them exhibited antiviral activity in the low micromolar range against SARS-CoV-2 and other human coronaviruses (HCoVs) in different cell lines. Time-of-addition experiments demo

SUBMITTER: Mercorelli B 

PROVIDER: S-EPMC9172283 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature