danДоклады Национальной академии наук БеларусиDoklady of the National Academy of Sciences of Belarus1561-83232524-2431The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"dan-421Research ArticleХИМИЯCHEMISTRYIN SILICO ДИЗАЙН И ОЦЕНКА ПОТЕНЦИАЛЬНОЙ АКТИВНОСТИ НОВЫХ ИНГИБИТОРОВ ВИЧ-1 − МИМЕТИКОВ ПЕРВИЧНОГО РЕЦЕПТОРА CD4 БЕЛКА GP120 ОБОЛОЧКИ ВИРУСАIN SILICO DESIGN AND EVALUATION OF THE POTENTIAL ACTIVITY OF NOVEL HIV-1 INHIBITORS – MIMETICS OF THE PRIMARY RECEPTOR CD4 OF THE VIRAL ENVELOPE GP120 PROTEINАндриановА. М.AndrianovA. M.

д-р хим. наук, гл. науч. сотрудник

D. Sc. (Chemistry), Chief researcher

andrianov@iboch.bas-net.byКашинИ. А.KashynI. A.

науч. сотрудник

Researcher

lighkia@gmail.comНиколаевГ. И.NikolaevG. I.

аспирант

Postgraduate student

reshaemsem@gmail.comТузиковА. В.TuzikovA. V.

член-корреспондент, д-р физ.-мат. наук, профессор, директор

Corresponding Member, D. Sc. (Physics and Mathematics), Professor, Director

tuzikov@newman.bas-net.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 Belarus2017150820176134757Copyright © Андрианов А.М., Кашин И.А., Николаев Г.И., Тузиков А.В., 20172017Андрианов А.М., Кашин И.А., Николаев Г.И., Тузиков А.В.Andrianov A.M., Kashyn I.A., Nikolaev G.I., 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/421

На основе методологии клик-химии осуществлен in silico дизайн новых ингибиторов проникновения ВИЧ-1, способных имитировать первичный рецептор CD4 белка gp120 оболочки вируса. С помощью методов молекулярного докинга проведена оценка нейтрализующей активности сконструированных молекул, в результате которой идентифицированы 6 соединений-лидеров, перспективных для синтеза и биологических испытаний. Показано, что обнаруженные соединения формируют базовые структуры для разработки новых эффективных анти-ВИЧ препаратов с широкой вирусной нейтрализацией. 

In silico design of novel HIV-1 entry inhibitors able to mimic the primary receptor CD4 of the viral envelope gp120 protein was carried out using the click-chemistry methodology. The neutralizing activity of the designed molecules was evaluated by molecular docking, resulting in the discovery of 6 top compounds promising for synthesis and biological trials. The designed compounds may be used as basic structures for the development of novel, potent, and safe antiviral drugs with broad HIV-1 neutralization.

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