farmaecFARMAKOEKONOMIKA. Modern Pharmacoeconomics and PharmacoepidemiologyФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология2070-49092070-4933IRBIS LLC10.17749/2070-4909/farmakoekonomika.2021.078farmaec-527Research ArticleORIGINAL ARTICLESОРИГИНАЛЬНЫЕ ПУБЛИКАЦИИChemoreactome screening of pharmaceutical effects on SARS-CoV-2 and human virome to help decide on drug-based COVID-19 therapyХемореактомный скрининг воздействия фармакологических препаратов на SARS-CoV-2 и виром человека как информационная основа для принятия решений по фармакотерапии COVID-19https://orcid.org/0000-0002-2659-7998ТоршинИ. Ю.TorshinI. Yu.

Торшин Иван Юрьевич – к.ф-м.н., к.х.н., старший научный сотрудник. Scopus Author ID: 7003300274; WoS ResearcherID: C-7683-2018; РИНЦ SPIN-код: 1375-1114

ул. Вавилова, д. 4, Москва 2119333, РоссияЛенинские Горы, д. 1, Москва 119991, Россия

Ivan Yu. Torshin – PhD (Phys. Math.), PhD (Chem.), Senior Researcher. Scopus Author ID: 7003300274; WoS ResearcherID: C-7683-2018; RSCI SPIN-code: 1375-1114

4 Vavilov Str., Moscow 2119333, Russia1 Leninskie Gory, Moscow 119991, Russia

https://orcid.org/0000-0002-7663-710XГромоваО. А.GromovaO. A.

Громова Ольга Алексеевна – д.м.н., профессор, научный руководитель; ведущий научный сотрудник. Scopus Author ID: 7003589812; WoS ResearcherID: J-4946-2017; РИНЦ SPIN-код: 6317-9833

ул. Вавилова, д. 4, Москва 2119333, РоссияЛенинские Горы, д. 1, Москва 119991, Россия

Olga A. Gromova – Dr. Med. Sc., Professor, Research Supervisor; Leading Researcher. Scopus Author ID: 7003589812; WoS ResearcherID: J-4946-2017; RSCI SPIN-code: 6317-9833

4 Vavilov Str., Moscow 2119333, Russia1 Leninskie Gory, Moscow 119991, Russia

unesco.gromova@gmail.comhttps://orcid.org/0000-0002-5070-5450ЧучалинА. Г.ChuchalinA. G.

Чучалин Александр Григорьевич – д.м.н., профессор, академик Российской академии наук, пульмонолог, заведующий кафедрой госпитальной терапии педиатрического факультета. РИНЦ SPIN-код: 7742-2054

ул. 1-я Леонова, д. 16, Москва 129226, Россия

Aleksandr G. Chuchalin – Dr. Med. Sc., Professor, Academician of the Russian Academy of Sciences, Pulmonologist, Head of Chair of Hospital Therapy, Faculty of Pediatrics. RSCI SPIN-code: 7742-2054

16 Pervaya Leonov Str., Moscow 129226, Russia

https://orcid.org/0000-0002-4911-8478ЖуравлевЮ. И.ZhuravlevYu. I.

Журавлев Юрий Иванович – д.мат.н., профессор, академик Российской академии наук, главный научный сотрудник. Scopus Author ID: 7005285135

ул. Вавилова, д. 4, Москва 2119333, Россия

Yuriy I. Zhuravlev – Dr. Math. Sc, Professor, Academician of RAS, Senior Researcher. Scopus Author ID: 7005285135

4 Vavilov Str., Moscow 2119333, Russia

Институт фармакоинформатики Федерального исследовательского центра «Информатика и управление» Российской академии наук; Центр хранения и анализа больших данных Федерального государственного бюджетного образовательного учреждения высшего образования «Московский государственный университет имени М.В. Ломоносова»РоссияInstitute of Pharmacoinformatics, Federal Research Center “Informatics and Management”, Russian Academy of Sciences; Big Data Storage and Analysis Center, Lomonosov Moscow State UniversityRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияPirogov Russian National Research Medical UniversityRussian FederationИнститут фармакоинформатики Федерального исследовательского центра «Информатика и управление» Российской академии наукРоссияInstitute of Pharmacoinformatics, Federal Research Center “Informatics and Management”, Russian Academy of SciencesRussian Federation202127072021142191–211Copyright © Torshin I.Y., Gromova O.A., Chuchalin A.G., Zhuravlev Y.I., 20212021Торшин И.Ю., Громова О.А., Чучалин А.Г., Журавлев Ю.И.Torshin I.Y., Gromova O.A., Chuchalin A.G., Zhuravlev Y.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacoeconomics.ru/jour/article/view/527Background

Background. So-called rational drug design is suboptimal when it comes to finding effective and safe drug-based treatment for COVID-19. Another approach seems promising: to reprofile the pharmaceuticals registered in the Anatomical, Therapeutic, and Chemical Classifier (ATC).

Material and methods

Material and methods. Chemoreactome screening, a method that simulates the results of inhibiting viral growth in a cell culture, models the effects of pharmaceuticals on the human virome, and estimates the adverse effects of medicines, was used to reprofile about 2700 pharmaceuticals from the ATC. The information technology behind chemoreactome analysis is based on the topological recognition theory advanced by the Institute of Pharmaceutical Informatics, Federal Research Center for Informatics and Control, Russian Academy of Sciences.

Results

Results. Sixty two pharmaceuticals and 20 micronutrients were found to have a pronounced antiviral effect with minimal side effects. Comparison against data of basic research and clinical trials showed 31 out of 62 pharmaceuticals to have been independently confirmed usable in COVID-19 treatment. These inhibit coronaviral proteins and/or function as adaptogenic molecules that improve the functioning of cells exposed to viral stress. Glucosamine sulfate was found to have the best safety profile and minimum effects on the healthy human virome out of all the tested anticoronaviral micronutrients.

Conclusions

Conclusions. Reprofiling of pharmaceuticals registered in the ATC could significantly speed up the search for more effective and safer drugbased COVID-19 treatments. Several micronutrients show promise for long-term coronavirus prevention, especially in the elderly.

Актуальность

Актуальность. Поиск эффективных и безопасных фармакологических подходов к лечению COVID-19 существенно затруднен в рамках так называемого рационального дизайна лекарств. Поэтому перспективно перепрофилирование лекарственных препаратов, зарегистрированных в анатомо-терапевтическо-химической классификации лекарств (АТХ).

Материал и методы

Материал и методы. Перепрофилирование около 2700 препаратов из АТХ проводилось методом хемореактомного скрининга, моделирующего результаты ингибирования роста вирусов в культуре клеток, воздействия препаратов на виром человека и оценки их побочных эффектов. Информационная технология хемореактомного анализа основана на топологической теории распознавания, развиваемой в Институте фармакоинформатики при Федеральном исследовательском центре «Информатика и управление» Российской академии наук.

Результаты

Результаты. Установлены 62 препарата и 20 микронутриентов, которые характеризуются выраженным противовирусным действием в сочетании с минимальными побочными эффектами. Сопоставление полученных результатов с данными фундаментальных и клинических исследований показало, что для 31 из 62 препаратов имеются независимые подтверждения целесообразности их использования для лечения COVID-19. Установленные препараты являются ингибиторами коронавирусных белков и/или молекулами- адаптогенами, улучшающими функционирование клеток в условиях стресса при вирусной инфекции. Среди изученных «антикоронавирусных» микронутриентов наилучшим профилем безопасности, в т.ч. минимальным воздействием на виром здоровых людей, обладал глюкозамина сульфат.

Заключение

Заключение. Перепрофилирование лекарственных препаратов, зарегистрированных в АТХ, может существенно ускорить нахождение более эффективных и безопасных подходов к фармакотерапии COVID-19. Перспективно применение ряда микронутриентов в программах долговременной профилактики коронавирусной инфекции, особенно у пожилых.

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