Comprehensive fitness landscape of SARS-CoV-2 M^pro reveals insights into viral resistance mechanisms.

ABSTRACT: With the continual evolution of new strains of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that are more virulent, transmissible, and able to evade current vaccines, there is an urgent need for effective anti-viral drugs. The SARS-CoV-2 main protease (M^pro) is a leading target for drug design due to its conserved and indispensable role in the viral life cycle. Drugs targeting M^pro appear promising but will elicit selection pressure for resistance. To understand resistance potential in M^pro, we performed a comprehensive mutational scan of the protease that analyzed the function of all possible single amino acid changes. We developed three separate high throughput assays of M^pro function in yeast, based on either the ability of M

SUBMITTER: Flynn JM 

PROVIDER: S-EPMC9323007 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature