Discovery of potent benzoxaborole inhibitors against SARS-CoV-2 main and dengue virus proteases.

ABSTRACT: The RNA viruses SARS-CoV-2 and dengue pose a major threat to human health worldwide and their proteases (M^pro; NS2B/NS3) are considered as promising targets for drug development. We present the synthesis and biological evaluation of novel benzoxaborole inhibitors of these two proteases. The most active compound achieves single-digit micromolar activity against SARS-CoV-2 M^pro in a biochemical assay. The most active substance against dengue NS2B/NS3 protease has submicromolar activity in cells (EC₅₀ 0.54 μM) and inhibits DENV-2 replication in cell culture. Most benzoxaboroles had no relevant cytotoxicity or significant off-target inhibition. Furthermore, the class demonstrated passive membrane penetration and stability against the evaluated proteases. This c

SUBMITTER: Kuhl N 

PROVIDER: S-EPMC9272583 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature