Potent and biostable inhibitors of the main protease of SARS-CoV-2.

ABSTRACT: Potent and biostable inhibitors of the main protease (M^pro) of SARS-CoV-2 were designed and synthesized based on an active hit compound 5h (2). Our strategy was based not only on the introduction of fluorine atoms into the inhibitor molecule for an increase of binding affinity for the pocket of M^pro and cell membrane permeability but also on the replacement of the digestible amide bond by a surrogate structure to increase the biostability of the compounds. Compound 3 is highly potent and blocks SARS-CoV-2 infection in vitro without a viral breakthrough. The derivatives, which contain a thioamide surrogate in the P2-P1 amide bond of these compounds (2 and 3), showed remarkably preferable pharmacokinetics in mice compared with the corr

SUBMITTER: Tsuji K 

PROVIDER: S-EPMC9623849 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature