Circadian clock modulating small molecules repurposing as inhibitors of SARS-CoV-2 Mpro for pharmacological interventions in COVID-19 pandemic.

The COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency warranting the development of targeted treatment. The main protease Mpro is considered as a key drug target in coronavirus infections because of its vital role in the proteolytic processing of two essential polyproteins required for the replication and transcription of viral RNA. Targeting and inhibiting the Mpro activity represents a valid approach to prevent the SARS-CoV-2 replication and spread. Based on the structure-assisted drug designing, here we report a circadian clock-modulating small molecule "SRT2183" as a potent inhibitor of Mpro to block the replication of SARS-CoV-2. The findings are expected to pave the way for the development of therapeutics for COVID-19.