Can Molecular Dynamics Explain Decreased Pathogenicity in Mutant Camphecene-Resistant Influenza Virus? | Sciact - CRIS-система Института катализа

Can Molecular Dynamics Explain Decreased Pathogenicity in Mutant Camphecene-Resistant Influenza Virus? Научная публикация

Журнал

Journal of Biomolecular Structure and Dynamics
ISSN: 1538-0254

Вых. Данные

Год: 2021, Том: 40, Номер: 12, Страницы: 5481-5492 Страниц : 12 DOI: 10.1080/07391102.2020.1871414

Ключевые слова

Camphecene-resistant influenza virus, hemagglutinin, camphecene, molecular docking, molecular dynamic

Авторы

Borisevich Sophia S. ¹ , Gureev Maxim A. ² , Yarovaya Оlga I. ³ , Zarubaev Vladimir V. ⁴ , Kostin Gennadiy A. ⁵ , Porozov Yuriy B. ^6,7,2 , Salakhutdinov Nariman F. ³

Организации

1	Laboratory of Physical Chemistry, Ufa Institute of Chemistry UFRS RAS, Ufa, Russia
2	Laboratory of Bioinformatics, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
3	Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch RAS, Novosibirsk, Russia
4	Department of Virology, Saint Petersburg Pasteur Institute, St. Petersburg, Russia
5	Nikolaev Institute of Inorganic Chemistry SB RAS, Novosibirsk, Russia
6	Department of Computational Biology, Sirius University of Science and Technology, Sochi, Russia
7	Department of Food Biotechnology and Engineering, ITMO University, St. Petersburg, Russia

The development of new anti-influenza drugs remains an active area, and efforts in this direction will likely continue far into the future. In this paper, we present the results of a theoretical study explaining the mechanisms behind the antiviral activity of camphor derivatives. These include camphecene and a number of its analogues. The compounds tested can inhibit hemagglutinin (HA) by binding to it at two possible sites. Moreover, the binding site located at the site of proteolysis is the most important. Serial passaging of influenza in the presence of camphecene leads to the formation of mutation-associated resistance. Specifically, camphecene causes a significant mutation in HA (V615L). This substitution likely reduces the affinity of the compound for the binding site due to steric restriction of the positioning of camphecene in the binding cavity. Molecular dynamics (MD) simulation results show that the mutant HA is a more stable structure in terms of thermodynamics. In other words, launching conformational rearrangements preceding the transition from pre- to post-fusion requires more energy than in wild type HA. This may well explain the lower virulence seen with the camphecene-resistant strain.

Borisevich S.S. , Gureev M.A. , Yarovaya О.I. , Zarubaev V.V. , Kostin G.A. , Porozov Y.B. , Salakhutdinov N.F.
Can Molecular Dynamics Explain Decreased Pathogenicity in Mutant Camphecene-Resistant Influenza Virus?
Journal of Biomolecular Structure and Dynamics. 2021. V.40. N12. P.5481-5492. DOI: 10.1080/07391102.2020.1871414 WOS Scopus CAPlus PMID OpenAlex

Поступила в редакцию:	24 сент. 2020 г.
Принята к публикации:	29 дек. 2020 г.
Опубликована online:	22 янв. 2021 г.

Web of science:	WOS:000609588300001
Scopus:	2-s2.0-85099741964
Chemical Abstracts:	2021:199650
PMID (PubMed):	33480324
OpenAlex:	W3122655214

БД	Цитирований
OpenAlex	15
Web of science	14
Scopus	11