Structure-Based Design, Synthesis, and Biological Evaluation of the Cage–Amide Derived Orthopox Virus Replication Inhibitors

Structure-Based Design, Synthesis, and Biological Evaluation of the Cage–Amide Derived Orthopox Virus Replication Inhibitors Full article

Journal

Viruses
ISSN: 1999-4915

Output data

Year: 2023, Volume: 15, Number: 1, Pages: 29 Pages count : 1 DOI: 10.3390/v15010029

Tags

adamantane; amides; antipox activity; p37

Authors

Mozhaitsev Evgenii S. ¹ , Suslov Evgeniy V. ¹ , Rastrepaeva Daria A. ¹ , Yarovaya Olga I. ¹ , Borisevich Sophia S. ² , Khamitov Edward M. ² , Kolybalov Dmitry S. ^3,4 , Arkhipov Sergey G. ^3,4 , Bormotov Nikolai I. ⁵ , Shishkina Larisa N. ⁵ , Serova Olga A. ⁵ , Brunilin Roman V. ⁶ , Vernigora Andrey A. ⁶ , Nawrozkij Maxim B. ⁷ , Agafonov Alexander P. ⁵ , Maksyutov Rinat A. ⁵ , Volcho Konstantin P. ¹ , Salakhutdinov Nariman F. ¹

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of Siberian Branch of Russian Academy of Sciences
2	Ufa Institute of Chemistry, RAS
3	Synchrotron Radiation Facility SKIF, G.K. Boreskov Institute of Catalysis SB RAS, Koltsovo, Russian Federation
4	Novosibirsk State University
5	State Research Center of Virology and Biotechnology VECTOR
6	Волгоградский государственный технический университет
7	Sirius University of Science and Technology, Sochi, 354349, Russian Federation

Despite the fact that the variola virus is considered eradicated, the search for new small molecules with activity against orthopoxviruses remains an important task, especially in the context of recent outbreaks of monkeypox. As a result of this work, a number of amides of benzoic acids containing an adamantane fragment were obtained. Most of the compounds demonstrated activity against vaccinia virus, with a selectivity index SI = 18,214 for the leader compound 18a. The obtained derivatives also demonstrated activity against murine pox (250 ≤ SI ≤ 6071) and cowpox (125 ≤ SI ≤ 3036). A correlation was obtained between the IC50 meanings and the binding energy to the assumed biological target, the p37 viral protein with R2 = 0.60.

Mozhaitsev E.S. , Suslov E.V. , Rastrepaeva D.A. , Yarovaya O.I. , Borisevich S.S. , Khamitov E.M. , Kolybalov D.S. , Arkhipov S.G. , Bormotov N.I. , Shishkina L.N. , Serova O.A. , Brunilin R.V. , Vernigora A.A. , Nawrozkij M.B. , Agafonov A.P. , Maksyutov R.A. , Volcho K.P. , Salakhutdinov N.F.
Structure-Based Design, Synthesis, and Biological Evaluation of the Cage–Amide Derived Orthopox Virus Replication Inhibitors
Viruses. 2023. V.15. N1. P.29. DOI: 10.3390/v15010029 WOS Scopus РИНЦ OpenAlex

Published print:	Jan 1, 2003
Submitted:	Dec 2, 2022
Accepted:	Dec 19, 2022
Published online:	Dec 21, 2022

Web of science:	WOS:000927718700001
Scopus:	2-s2.0-85147045547
Elibrary:	54497692
OpenAlex:	W4313533516

DB	Citing
OpenAlex	12
Web of science	8
Scopus	6