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

0556963 - ÚOCHB 2023 RIV CH eng J - Journal Article
Konkoľová, Eva - Krejčová, Kateřina - Eyer, L. - Hodek, Jan - Zgarbová, Michala - Fořtová, A. - Jirásek, Michael - Teplý, Filip - Reyes Gutierrez, Paul Eduardo - Růžek, Daniel - Weber, Jan - Bouřa, Evžen
A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases.
Molecules. Roč. 27, č. 6 (2022), č. článku 1894. E-ISSN 1420-3049
R&D Projects: GA ČR(CZ) GA21-25280S; GA MZd(CZ) NU20-05-00472; GA MŠMT(CZ) LTAUSA18016
Institutional support: RVO:61388963 ; RVO:60077344
Keywords : helquat-like compound * RNA-dependent RNA-polymerase * SARS-CoV-2 * flaviruses * antiviral agents
OECD category: Biochemistry and molecular biology; Microbiology (BC-A)
Impact factor: 4.6, year: 2022
Method of publishing: Open access
https://doi.org/10.3390/molecules27061894

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.
Permanent Link: http://hdl.handle.net/11104/0331081