Dissecting the Binding Affinity of Anti-SARS-CoV-2 Compounds to Human Transmembrane Protease, Serine 2: A Computational Study.

ABSTRACT: The human transmembrane protease, serine 2 (TMPRSS2), essential for SARS-CoV-2 entry, is a key antiviral target. Here, we computationally profiled the TMPRSS2-binding affinities of 15 antiviral compounds. Molecular dynamics (MD) simulations for the docked complexes revealed that three compounds exited the substrate-binding cavity (SBC), suggesting noncompetitive inhibition. Of the remaining compounds, five charged ones exhibited reduced binding stability due to competing electrostatic interactions and increased solvent exposure, while seven neutral compounds showed stronger binding affinity driven by van der Waals (vdW) interactions compensating for unfavorable electrostatic effects (including electrostatic interactions and desolvation penalties). Positive and negative hotspot residues wer

SUBMITTER: Shi YH 

PROVIDER: S-EPMC11766390 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature