Quaternary ammonium salts based on (-)-borneol as effective inhibitors of influenza virus

Quaternary ammonium salts based on (-)-borneol as effective inhibitors of influenza virus Full article

Journal

Archives of Virology
ISSN: 0304-8608

Output data

Year: 2021, Volume: 166, Pages: 1965–1976 Pages count : DOI: 10.1007/s00705-021-05102-1

Authors

Sokolova Anastasiya S. ¹ , Yarovaya Olga I. ¹ , Baranova Darya V. ¹ , Galochkina Anastasia V. ² , Shtro Anna A. ³ , Kireeva Marina V. ⁴ , Borisevich Sophia S. ⁵ , Gatilov Yuriy V. ¹ , Zarubaev Vladimir V. ² , Salakhutdinov Nariman F. ¹

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, Novosibirsk, 630090, Russian Federation
2	Pasteur Institute of Epidemiology and Microbiology, 14 Mira str., St. Petersburg, 197101, Russian Federation
3	Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., St. Petersburg, 197376, Russian Federation
4	Saint Petersburg State University, 7/9 Universitetskaya nab., St. Petersburg, 199034, Russian Federation
5	Laboratory of Chemical Physics, Ufa Institute of Chemistry Ufa Federal Research Center, 71 Pr. Oktyabrya, Ufa, 450078, Russian Federation

A series of compounds containing a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment were evaluated for their antiviral activity against influenza A virus strain A/Puerto Rico/8/34 (H1N1) in vitro. The most potent antiviral compound proved to be a quaternary ammonium salt based on (-)-borneol, 10a. In in vitro experiments, compound 10a inhibited influenza A viruses (H1, H1pdm09, and H3 subtypes), with an IC50 value of 2.4-16.8 µM (depending on the virus), and demonstrated low toxicity (CC50 = 1311 µM). Mechanism-of-action studies for compound 10a revealed it to be most effective when added at the early stages of the viral life cycle. In direct haemolysis inhibition tests, compound 10a was shown to decrease the membrane-disrupting activity of influenza A virus strain A/Puerto Rico/8/34. According to molecular modelling results, the lead compound 10a can bind to different sites in the stem region of the viral hemagglutinin. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.

Sokolova A.S. , Yarovaya O.I. , Baranova D.V. , Galochkina A.V. , Shtro A.A. , Kireeva M.V. , Borisevich S.S. , Gatilov Y.V. , Zarubaev V.V. , Salakhutdinov N.F.
Quaternary ammonium salts based on (-)-borneol as effective inhibitors of influenza virus

Archives of Virology. 2021. V.166. P.1965–1976. DOI: 10.1007/s00705-021-05102-1 WOS Scopus РИНЦ

Full text from publisher

Published online:	May 13, 2021
Published print:	Jul 1, 2021

Web of science	WOS:000650114800005
Scopus	2-s2.0-85105658155
Elibrary	46055619
OpenAlex	W3134141506