Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses? | Sciact - CRIS-система Института катализа

Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses? Научная публикация

Журнал

International Journal of Molecular Sciences
ISSN: 1422-0067 , E-ISSN: 1661-6596

Вых. Данные

Год: 2022, Том: 23, Номер: 14, Номер статьи : 7721, Страниц : 14 DOI: 10.3390/ijms23147721

Ключевые слова

flavivirus; TBEV; WNV; ZIKV; DENV; monoclonal antibody; recombinant protein; ELISA; molecular protein docking; molecular protein dynamic

Авторы

Shanshin Daniil V. ¹ , Borisevich Sophia S. ^2,3 , Bondar Alexander A. ⁴ , Porozov Yuri B. ^5,6 , Rukhlova Elena A. ¹ , Protopopova Elena V. ¹ , Ushkalenko Nikita D. ¹ , Loktev Valery B. ¹ , Chapoval Andrei I. ³ , Ilyichev Alexander A. ¹ , Shcherbakov Dmitriy N. ¹

Организации

1	State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia
2	Laboratory of Physical Chemistry, Ufa Institute of Chemistry, Ufa Federal Research Center Russian Academy of Science, 450054 Ufa, Russia
3	Russian-American Anti-Cancer Center, Altai State University, 656049 Barnaul, Russia
4	Institute of Chemical Biology and Fundamental Medicine, 630090 Novosibirsk, Russia
5	Department of Computational Biology, Sirius University of Science and Technology, Olympic Ave 1, 354340 Sochi, Russia
6	The Center of Bio- and Chemoinformatics, I.M. Sechenov First Moscow State Medical University, 119435 Moscow, Russia

Flaviviruses are single-stranded RNA viruses that have emerged in recent decades and infect up to 400 million people annually, causing a variety of potentially severe pathophysiological processes including hepatitis, encephalitis, hemorrhagic fever, tissues and capillaries damage. The Flaviviridae family is represented by four genera comprising 89 known virus species. There are no effective therapies available against many pathogenic flaviviruses. One of the promising strategies for flavivirus infections prevention and therapy is the use of neutralizing antibodies (NAb) that can disable the virus particles from infecting the host cells. The envelope protein (E protein) of flaviviruses is a three-domain structure that mediates the fusion of viral and host membranes delivering the infectious material. We previously developed and characterized 10H10 mAb which interacts with the E protein of the tick-borne encephalitis virus (TBEV) and many other flaviviruses’ E proteins. The aim of this work was to analyze the structure of E protein binding sites recognized by the 10H10 antibody, which is reactive with different flavivirus species. Here, we present experimental data and 3D modeling indicating that the 10H10 antibody recognizes the amino acid sequence between the two cysteines C92-C116 of the fusion loop (FL) region of flaviviruses’ E proteins. Overall, our results indicate that the antibody-antigen complex can form a rigid or dynamic structure that provides antibody cross reactivity and efficient interaction with the fusion loop of E protein.

Shanshin D.V. , Borisevich S.S. , Bondar A.A. , Porozov Y.B. , Rukhlova E.A. , Protopopova E.V. , Ushkalenko N.D. , Loktev V.B. , Chapoval A.I. , Ilyichev A.A. , Shcherbakov D.N.
Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses?
International Journal of Molecular Sciences. 2022. V.23. N14. 7721 :1-14. DOI: 10.3390/ijms23147721 WOS Scopus РИНЦ CAPlusCA PMID OpenAlex

Поступила в редакцию:	11 июн. 2022 г.
Принята к публикации:	11 июл. 2022 г.
Опубликована в печати:	13 июл. 2022 г.

Web of science:	WOS:000833147200001
Scopus:	2-s2.0-85135123484
РИНЦ:	56143001
Chemical Abstracts:	2022:1991388
Chemical Abstracts (print):	179:328536
PMID (PubMed):	35887069
OpenAlex:	W4285496143

БД	Цитирований
OpenAlex	6
Web of science	5
Scopus	5