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

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 mu M) and inhibits DENV-2 replication in cell culture. Most benzoxaboroles had no relevant cytotoxicity or significant offtarget inhibition. Furthermore, the class demonstrated passive membrane penetration and stability against the evaluated proteases. This compound class may contribute to the development of antiviral agents with activity against DENV or SARS-CoV-2.

Automated summary

This study synthesized novel benzoxaborole inhibitors and evaluated their biological activity against the proteases of SARS-CoV-2 and dengue viruses. The most active compound showed strong inhibition against SARS-CoV-2 and significant inhibitory effects against dengue virus replication in cells.