Mechanism of non-competitive inhibition of the SARS-CoV-2 3CL protease dimerization: Therapeutic and clinical promise of the lichen secondary metabolite perlatolinic acid.

ABSTRACT: In response to the COVID-19 pandemic, identifying effective treatments against SARS-CoV-2 has become of utmost importance. This study elucidates the mechanism by which perlatolinic acid, a lichen-derived secondary metabolite, non-competitively inhibits the dimerization of the SARS-CoV-2 3CL protease, a pivotal enzyme in the virus lifecycle. Utilising a combination of kinetic parameter determination, inhibition assays, and molecular docking studies, we demonstrate that perlatolinic acid effectively disrupts the enzymatic function by binding at the dimer interface with a measured K _i value of 0.67 μM, thereby impeding the protease catalytic activity essential for viral replication. Molecular docking studies further corroborate the binding specificity of perlatolinic

SUBMITTER: Fagnani L 

PROVIDER: S-EPMC11471173 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature