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

E. Konkolova, K. Krejčová, L. Eyer, J. Hodek, M. Zgarbová, A. Fořtová, M. Jirasek, F. Teply, PE. Reyes-Gutierrez, D. Růžek, J. Weber, E. Boura

. 2022 ; 27 (6) : . [pub] 20220315

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc22010765

Grant support
21-25280S Czech Science Foundation

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.

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$a 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.
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