Korupensamine A, but not its atropisomer, korupensamine B, inhibits SARS-CoV-2 in vitro by targeting its main protease (M^pro).

ABSTRACT: By combining docking and molecular dynamics simulations, we explored a library of 65 mostly axially chiral naphthylisoquinoline alkaloids and their analogues, with most different molecular architectures and structural analogues, for their activity against SARS-CoV-2. Although natural biaryls are often regarded without consideration of their axial chirality, they can bind to protein targets in an atroposelective manner. By combining docking results with steered molecular dynamics simulations, we identified one alkaloid, korupensamine A, that atropisomer-specifically inhibited the main protease (M^pro) activity of SARS-CoV-2 significantly in comparison to the reference covalent inhibitor GC376 (IC₅₀ = 2.52 ± 0.14 and 0.88 ± 0.15 μM, respectively) and reduced viral growth

SUBMITTER: Sayed AM 

PROVIDER: S-EPMC9972725 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature