A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases

• Autoři: KONKOLOVA Eva; KREJČOVÁ Kateřina; EYER Luděk; HODEK Jan; ZGARBOVÁ Michala; FOŘTOVÁ Andrea; JIRASEK Michael; TEPLY Filip; REYES-GUTIERREZ Paul E.; RŮŽEK Daniel; WEBER Jan; BOURA Evzen
• Rok publikování: 2022
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: Molecules
• Fakulta / Pracoviště MU: Přírodovědecká fakulta
• www: https://www.mdpi.com/1420-3049/27/6/1894
• Doi: https://doi.org/10.3390/molecules27061894
• Klíčová slova: helquat-like compound; RNA-dependent RNA-polymerase; SARS-CoV-2; Flaviruses; antiviral agents
• Popis: Positive-sense single-stranded RNA (+RNA) viruses have proven to be important pathogens that are able to threaten and deeply damage modern societies, as illustrated by the ongoing COVID-19 pandemic. Therefore, compounds active against most or many +RNA viruses are urgently needed. Here, we present PR673, a helquat-like compound that is able to inhibit the replication of SARS-CoV-2 and tick-borne encephalitis virus in cell culture. Using in vitro polymerase assays, we demonstrate that PR673 inhibits RNA synthesis by viral RNA-dependent RNA polymerases (RdRps). Our results illustrate that the development of broad-spectrum non-nucleoside inhibitors of RdRps is feasible.