Nashaat T. Nashed

Abstract We investigate the effects of two naturally selected substitution and deletion (Δ) mutations, constituting part of the substrate binding subsites S2 and S4, on the structure, function, and inhibition of SARS CoV-2 main protease. Comparable to wild-type, MProD48Y/ΔP168 undergoes N-terminal autoprocessing essential for stable dimer formation and mature-like catalytic activity.

Abstract A critical step for SARS-CoV-2 assembly and maturation involves the autoactivation of the main protease (MProWT) from precursor polyproteins. Upon expression, a model precursor of MProWT mediates its own release at its termini rapidly to yield a mature dimer. A construct with an E290A mutation within MPro exhibits time dependent autoprocessing of the accumulated precursor at the N-terminal nsp4/nsp5 site followed by the C-terminal nsp5/nsp6 cleavage.