Interaction of the new inhibitor paxlovid (PF-07321332) and ivermectin with the monomer of the main protease SARS-CoV-2: A volumetric study based on molecular dynamics, elastic networks, classical thermodynamics and SPT.

ABSTRACT: The COVID-19 pandemic has accelerated the study of drugs, most notably ivermectin and more recently Paxlovid (PF-07321332) which is in phase III clinical trials with experimental data showing covalent binding to the viral protease M^pro. Theoretical developments of catalytic site-directed docking support thermodynamically feasible non-covalent binding to M^pro. Here we show that Paxlovid binds non-covalently at regions other than the catalytic sites with energies stronger than reported and at the same binding site as the ivermectin B1a homologue, all through theoretical methodologies, including blind docking. We volumetrically characterize the non-covalent interaction of the ivermectin homologues (avermectins B1a and B1b) and Paxlovid with the mM^pro monomer,

SUBMITTER: Alvarado YJ 

PROVIDER: S-EPMC9107165 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature