(+)-Usnic Acid and Its Derivatives as Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses

Aleksandr S Filimonov; Olga I Yarovaya; Anna V Zaykovskaya; Nadezda B Rudometova; Dmitriy N Shcherbakov; Varvara Yu Chirkova; Dmitry S Baev; Sophia S Borisevich; Olga A Luzina; Oleg V Pyankov; Rinat A Maksyutov; Nariman F Salakhutdinov

doi:10.3390/v14102154

(+)-Usnic Acid and Its Derivatives as Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses

Viruses. 2022 Sep 29;14(10):2154. doi: 10.3390/v14102154.

Affiliations

¹ Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia.
² State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Yekaterinburg, Russia.
³ Department of Physical-Chemistry Biology and Biotechnology, Altay State University, 656049 Barnaul, Russia.
⁴ Laboratory of Chemical Physics, Ufa Institute of Chemistry Ufa Federal Research Center, 450078 Ufa, Russia.

Abstract

In order to test the antiviral activity, a series of usnic acid derivatives were synthesized, including new, previously undescribed compounds. The activity of the derivatives against three strains of SARS-CoV-2 virus was studied. To understand the mechanism of antiviral action, the inhibitory activity of the main protease of SARS-CoV-2 virus was studied using the developed model as well as the antiviral activity against the pseudoviral system with glycoprotein S of SARS-CoV-2 virus on its surface. It was shown that usnic acid exhibits activity against three strains of SARS-CoV-2 virus: Wuhan, Delta, and Omicron. Compounds 10 and 13 also showed high activity against the three strains. The performed biological studies and molecular modeling allowed us to assume that the derivatives of usnic acid bind in the N-terminal domain of the surface glycoprotein S at the binding site of the hemoglobin decay metabolite.

Keywords: antiviral compound; main viral protease 3CLPro; molecular modeling; surface glycoprotein S; usnic acid; virus SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / chemistry
Antiviral Agents / pharmacology
COVID-19*
Humans
Membrane Glycoproteins
Molecular Docking Simulation
Peptide Hydrolases
Protease Inhibitors / pharmacology
SARS-CoV-2*

Substances

usnic acid
Protease Inhibitors
Antiviral Agents
Peptide Hydrolases
Membrane Glycoproteins

Grants and funding

This work was supported by the Russian Science Foundation grant 22-23-00618.