Analogs of the Catechol Derivative Dynasore Inhibit HIV-1 Ribonuclease H, SARS-CoV-2 nsp14 Exoribonuclease, and Virus Replication

Viral replication often depends on RNA maturation and degradation processes catalyzed by viral ribonucleases, which are therefore candidate targets for antiviral drugs. Here, we synthesized studied the properties of a novel nitrocatechol compound (1c) other analogs that structurally related to catechol derivative dynasore. Interestingly, 1c strongly inhibited two DEDD box HIV-1 RNase H SARS-CoV-2 nsp14 3′-to-5′ exoribonuclease (ExoN). While ExoN activity, it did not interfere with mRNA methyltransferase activity nsp14. In silico molecular docking placed in catalytic pocket domain Finally, but had no toxicity human lung adenocarcinoma cells. Given its simple chemical synthesis from easily available starting materials, these results suggest might be lead design new compounds target coronavirus ribonucleases.