Simulation of Molecular Dynamics of SARS‐CoV‐2 S‐Protein in the Presence of Multiple Arbidol Molecules: Interactions and Binding Mode Insights

Simulation of Molecular Dynamics of SARS‐CoV‐2 S‐Protein in the Presence of Multiple Arbidol Molecules: Interactions and Binding Mode Insights Научная публикация

Журнал

Viruses
ISSN: 1999-4915

Вых. Данные

Год: 2022, Том: 14, Номер: 1, Номер статьи : 119, Страниц : DOI: 10.3390/v14010119

Ключевые слова

Arbidol; Coronavirus surface protein S‐spike; Molecular docking; Molecular dynamics; Pseudoviral system; SARS‐CoV‐2

Авторы

Borisevich S.S. ¹ , Khamitov E.M. ¹ , Gureev M.A. ^2,3 , Yarovaya O.I. ⁴ , Rudometova N.B. ⁵ , Zybkina A.V. ⁵ , Mordvinova E.D. ⁴ , Shcherbakov D.N. ⁵ , Maksyutov R.A. ⁵ , Salakhutdinov N.F. ⁴

Организации

1	Ufa Federal Research Center, Laboratory of Chemical Physics Ufa Institute of Chemistry, RAS, Octyabrya pr., 71, Ufa, 450054, Russian Federation
2	Research Center “Digital Biodesign and Personalized Healthcare”, I.M. Sechenov First Moscow State Medical University, Moscow, 119991, Russian Federation
3	Department of Computational Biology, Sirius University of Science and Technology, Sochi, 354349, Russian Federation
4	Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrent’ev Av., Novosibirsk, 630090, Russian Federation
5	State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, Koltsovo, Novosibirsk, 630559, Russian Federation

In this work, we evaluated the antiviral activity of Arbidol (Umifenovir) against SARS‐CoV‐2 using a pseudoviral system with the glycoprotein S of the SARS‐CoV‐2 virus on its surface. In order to search for binding sites to protein S of the virus, we described alternative binding sites of Arbidol in RBD and in the ACE‐2‐RBD complex. As a result of our molecular dynamics simulations combined with molecular docking data, we note the following fact: wherever the molecules of Arbidol bind, the interaction of the latter affects the structural flexibility of the protein. This interaction may result both in a change in the shape of the domain–enzyme binding interface and simply in a change in the structural flexibility of the domain, which can subsequently affect its affinity to the enzyme. In addition, we examined the possibility of Arbidol binding in the stem part of the surface protein. The possibility of Arbidol binding in different parts of the protein is not excluded. This may explain the antiviral activity of Arbidol. Our results could be useful for researchers searching for effective SARS‐CoV‐2 virus inhibitors targeting the viral entry stage. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Borisevich S.S. , Khamitov E.M. , Gureev M.A. , Yarovaya O.I. , Rudometova N.B. , Zybkina A.V. , Mordvinova E.D. , Shcherbakov D.N. , Maksyutov R.A. , Salakhutdinov N.F.
Simulation of Molecular Dynamics of SARS‐CoV‐2 S‐Protein in the Presence of Multiple Arbidol Molecules: Interactions and Binding Mode Insights
Viruses. 2022. V.14. N1. 119 . DOI: 10.3390/v14010119 WOS Scopus

Web of science	WOS:000749830700001
Scopus	2-s2.0-85122799818
OpenAlex	W4205305236