Modulation of the monomer-dimer equilibrium and catalytic activity of SARS-CoV-2 main protease by a transition-state analog inhibitor

Abstract

The binding of a drug targeting the active site of a predominantly monomeric SARS-CoV-2 main protease (MProM) favors an equilibrium shift to MProM dimer formation with two equivalent active sites. These results suggest targeting the monomeric active site and/or the dimer interface to interfere with the conformational rearrangements to active dimer formation as an alternative drug design strategy against MPro.