pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2026-14-3-297-306pmedpharm-1897Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯRESEARCH ARTICLEФитохимическое профилирование и оценка in silico соединений Mentha pulegium L. против метилтрансферазы VP39 вируса оспы обезьянPhytochemical profiling and in silico evaluation of Mentha pulegium L. compounds againstmonkeypox virus methyltransferase VP39https://orcid.org/0000-0002-6008-3325БудуФ.BoudouF.

доктор философии, кафедра прикладной молекулярной генетики, факультет естественных и биологических наук, Университет науки и технологий Орана (Алжир). 

BP 1505, Бир-эль-Джир 31000, Оран, Алжир.

Doctor of Philosophy, Department of Applied Molecular Genetics, Faculty of Natural and Life Sciences, University of Science and Technology of Oran (Algeria).

BP 1505, Bir El Djir 31000, Oran, Algeria.

farouk.boudou@univ-usto.dzhttps://orcid.org/0000-0003-0997-690XБелакредарА.BelakredarA.

доктор биотехнологии, доцент кафедры биотехнологии факультета естественных наук и жизни, Университет Мостаганема (Алжир). 

Национальный маршрут № 11, Харуба, Мостаганем, 27000, Алжир.

Doctor of Biotechnology, Assistant Professor, Department of Biotechnology, Faculty of Natural Sciences and Life, University of Mostaganem (Algeria). 

Route Nationale N 11, Kharouba, Mostaganem 27000.

belakredar-amel@hotmail.frУниверситет науки и технологий Орана.АлжирUniversity of Science and Technology of Oran.AlgeriaУниверситет Мостаганема.АлжирUniversity of Mostaganem.Algeria202618062026143297306Copyright © Буду Ф., Белакредар А., 20262026Буду Ф., Белакредар А.Boudou F., Belakredar A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/1897

В исследовании изучен потенциал биологически активных соединений Mentha pulegium L. в качестве ингибиторов метилтрансферазы VP39 вируса оспы обезьян. Для идентификации и характеристики фенольных соединений в растительном экстракте была использована высокоэффективная жидкостная хроматография (ВЭЖХ). Вычислительные методы были использованы для прогнозирования сходства и токсичности лекарственных средств, а также для оценки энергий связывания с помощью молекулярного докинга и моделирования динамики.

Цель

Цель. Изучить противовирусный потенциал соединений M. pulegium против вируса оспы обезьян VP39 путем оценки их сходства с лекарственными препаратами, токсичности и стабильности связывания с помощью вычислительных методов.

Материалы и методы

Материалы и методы. Различные фенольные соединения M. pulegium идентифицированы с помощью ВЭЖХ. Сходство с лекарственными препаратами и токсичность предсказаны с помощью SwissADME, ProTox 3.0 и OSIRIS Property Explorer. С помощью молекулярного докинга оценивали сродство выбранных соединений к VP39, а моделирование молекулярной динамики позволило оценить стабильность этих связей с течением времени.

Результаты

Результаты. Лютеолин и розмариновая кислота продемонстрировали наилучшую степень связывания с VP39, составив –9,3 и –8,7 ккал/моль соответственно, а также образовывали множественные водородные связи с ключевыми аминокислотными остатками: Ile94, Gly96, Phe115, Val139, Ala158, Lys186 и Tyr189 для лютеолина; Gly68, Ile94, Asp95, Val112, Phe115, Val141 и Asn156 для розмариновой кислоты. Моделирование молекулярной динамики показало, что лютеолин и розмариновая кислота взаимодействуют с умеренно гибкими участками фермента (остатки 67–79 и 243–246), при этом RMSD стабилизируется на уровне около 3,91 Å после 5000 пс, что повышает стабильность связывания и свидетельствует о сильном потенциале ингибирующей активности.

Заключение

Заключение. Полученные данные подчёркивают потенциал лютеолина и розмариновой кислоты M. pulegium в качестве перспективных противовирусных веществ в борьбе с вирусом оспы обезьян. Данное исследование является основой для дальнейшего изучения и разработки новых терапевтических стратегий, основанных на этих природных соединениях.

This study explores the potential of bioactive compounds from Mentha pulegium L. as inhibitors of the monkeypox virus methyltransferase VP39. High-Performance Liquid Chromatography (HPLC) was employed to identify and characterize phenolic compounds in the plant extract. Computational methods were used to predict drug-likeness and toxicity and to evaluate binding interactions through molecular docking and dynamics simulations.

The aim

The aim. To investigate the antiviral potential of M. pulegium compounds against monkeypox virus VP39 by evaluating their drug-likeness, toxicity, and interaction stability through computational approaches.

Materials and methods

Materials and methods. Various phenolic compounds in M. pulegium were identified using HPLC. Drug-likeness and toxicity were predicted using SwissADME, ProTox 3.0 Tool, and OSIRIS Property Explorer tools. Molecular docking studies assessed the binding affinity of selected compounds with VP39, and molecular dynamics simulations evaluated the stability of these interactions over time.

Results

Results. Luteolin and rosmarinic acid exhibited the highest binding affinities to VP39, with docking scores of −9.3 kcal/mol and −8.7 kcal/mol, respectively, and formed multiple hydrogen bonds with key amino acid residues including Ile94, Gly96, Phe115, Val139, Ala158, Lys186, and Tyr189 for luteolin, and Gly68, Ile94, Asp95, Val112, Phe115, Val141, and Asn156 for rosmarinic acid. Molecular dynamics simulations showed that these compounds interacted with moderately flexible regions of the enzyme (residues 67–79 and 243–246), with the RMSD stabilizing at around 3.91 Å after 5000 ps, enhancing binding stability and suggesting a strong potential for inhibitory activity.

Conclusion

Conclusion. The findings underscore the potential of luteolin and rosmarinic acid from M. pulegium as promising antiviral agents against the monkeypox virus. This research provides a foundation for further exploration and development of novel therapeutic strategies based on these natural compounds.

Mentha pulegium L.вирус оспы обезьянметилтрансфераза VP39молекулярный докингмолекулярная динамикасходство с лекарственными препаратамитоксичностьMentha pulegium L.monkeypox virusmethyltransferase VP39molecular dockingmolecular dynamicsdrug-likenesstoxicity assessmentДанное исследование не имело финансовой поддержки от сторонних организаций.This study did not have financial support from third-party organizations.ReferencesTaku A.K., Bhat M.A., Dutta T., Chhabra R. Viral diseases transmissible from non-human primates to man // Indian J Virol. – 2007. – Vol. 18, No. 2. – P. 47–56.Taku AK, Bhat MA, Dutta T, Chhabra R. Viral diseases transmissible from non-human primates to man. Indian J Virol. 2007;18(2):47–56.Adalja A., Inglesby T. A novel international monkeypox outbreak // Ann Intern Med. – 2022. – Vol. 175, No. 10. – P. 1490–1492. DOI: 10.7326/M22-1581Adalja A, Inglesby T. A novel international monkeypox outbreak. Ann Intern Med. 2022;175(10):1490–2. DOI: 10.7326/M22-1581Ligon B.L. 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The authors declare that there are no conflicts of interest present.