danДоклады Национальной академии наук БеларусиDoklady of the National Academy of Sciences of Belarus1561-83232524-2431The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8323-2022-66-2-156-166dan-1050Research ArticleХИМИЯCHEMISTRYIn silico скрининг потенциальных ингибиторов SARS-CoV-2, блокирующих тример HR1 белка S коронавирусаIn silico screening of the potential SARS-CoV-2 inhibitors blocking the HR1 trimer of the coronavirus protein SАндриановА. М.AndrianovA. M.

Андрианов Александр Михайлович – доктор химических наук, главный научный сотрудник

ул. Купревича, 5/2, 220141

Andrianov Alexander M. – D. Sc. (Chemistry)

5/2, Kuprevich Str., 220141, Minsk

andrianov@iboch.byФурсК. В.FursK. V.

Фурс Константин Викторович – инженер-программист

ул. Сурганова, 6, 220012, Минск

 

Furs Konstantin V. – Software Engineer

6, Surganov Str., 220012

ky6ujlo@gmail.comЮшкевичА. М.YushkevichA. M.

Юшкевич Артемий Михайлович – стажер младший научный сотрудника

ул. Сурганова, 6, 220012, Минск

Yushkevich Artsemi M. – Trainee of Junior Researcher

6, Surganov Str., 220012

geneprog@gmail.comГончарА. В.GoncharA. V.

Гончар Анна Викторовна – стажер младший научный сотрудника

ул. Сурганова, 6, 220012, Минск

Gonchar Anna V. – Trainee of Junior Researcher

6, Surganov Str., 220012

raphaelkyzy@gmail.comТузиковА. В.TuzikovA. V.

Тузиков Александр Васильевич – член-корреспондент, доктор физико-математических наук, профессор, заведующий лабораторией

ул. Сурганова, 6, 220012, Минск

Tuzikov Alexander V. – Corresponding Member, D. Sc. (Physics and Mathematics), Professor, Head of the Laboratory

6, Surganov Str., 220012

tuzikov@newman.basnet.byИнститут биоорганической химии Национальной академии наук БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of BelarusОбъединенный институт проблем информатики Национальной академии наук БеларусиUnited Institute of Informatics Problems of the National Academy of Sciences of Belarus202206052022662156166Copyright © Андрианов А.М., Фурс К.В., Юшкевич А.М., Гончар А.В., Тузиков А.В., 20222022Андрианов А.М., Фурс К.В., Юшкевич А.М., Гончар А.В., Тузиков А.В.Andrianov A.M., Furs K.V., Yushkevich A.M., Gonchar A.V., Tuzikov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://doklady.belnauka.by/jour/article/view/1050

Сформирована виртуальная библиотека биологически активных молекул и осуществлен in silico скрининг низкомолекулярных химических соединений – потенциальных ингибиторов SARS-CoV-2, способных связываться с тримером HR1 белка S и блокировать образование 6-спирального пучка 6-HB (six-helix bundle), критического для слияния мембран вируса и клетки-мишени и его инфективности. Методами молекулярного моделирования выполнена оценка эффективности связывания идентифицированных соединений с тримером HR1 белка S. В результате обнаружены 12 молекул, характеризующихся высокой аффинностью связывания с этим функционально важным участком оболочки вируса. Полученные данные свидетельствуют о перспективности использования этих соединений в работах по созданию новых противовирусных препаратов – ингибиторов слияния SARSCoV-2, которые могут блокировать проникновение вируса в клетку хозяина.

A virtual library of biologically active molecules has been formed and in silico screening has been carried out for identification of small-molecule chemical compounds – potential SARS-CoV-2 inhibitors able to bind to the HR1 trimer of the protein S and to block the formation of a six-helix bundle 6-HB, which is critical for the virus-cell fusion and viral infectivity. Molecular modeling methods were used to evaluate the binding affinity of the identified compounds to the HR1 trimer of the protein S. As a result, 12 molecules exhibiting the high binding affinity to this functionally important region of the virus were found. The data obtained indicate the promise of using these compounds in the development of new antiviral drugs presenting SARS-CoV-2 fusion inhibitors that can block the virus entry into the host cell.

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The authors declare that there are no conflicts of interest present.