New insights in the mechanism of the SARS-CoV-2 M^pro inhibition by benzisoselenazolones and diselenides.

ABSTRACT: Although global vaccination campaigns alleviated the SARS-CoV-2 pandemic in terms of morbidity and mortality, the ability of the virus to originate mutants may reduce the efficacy of vaccines, posing a serious risk of a renewed pandemic. There is therefore a need to develop small molecules capable of targeting conserved viral targets, such as the main protease (M^pro). Here, a series of benzisoselenazolones and diselenides were tested for their ability to inhibit M^pro; then the most potent compounds were measured for antiviral activity in vitro, and the mechanism of action was investigated. Density functional theory calculations, molecular docking and molecular dynamics simulations were also used to elucidate the protein/drug interaction. Finally, a bio-organic model w

SUBMITTER: Sancineto L 

PROVIDER: S-EPMC11494035 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature