Developing inhibitors of the SARS-CoV-2 main protease

Abstract

SARS-CoV-2 is the causative virus of the global pandemic disease COVID-19, causing a significant public health burden. With the continued spread of SARS-CoV-2 comes an urgent need for drugs to treat those infected. The main protease (Mpro, also known as 3CL) of SARS-CoV-2 is a validated drug target. We created a pipeline to computationally screen molecules on a variety of Mpro pockets and pocket sizes, identified with enhanced sampling molecular dynamics simulations before carrying the putative hits forward to in vitro and in vivo assays for hit validation and optimization.