A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases
MOLECULES(2022)
Abstract
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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Key words
helquat-like compound, RNA-dependent RNA-polymerase, SARS-CoV-2, Flaviruses, antiviral agents
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