WOS: QUARTILE 1 

Open Access

В журнале  European Journal of Pharmacology (Издательство  MDPI, IF 4,2) по результатам работы, выполненной совместно с коллегами из Института Гриппа (Санкт-Петербург), ЦКП "СКИП" (Кольцово) и НГУ, опубликована статья, соавторами которой является сотрудники Института: к.х.н. К.С. Ковалева (снс ЛФАВ), д.х.н. О.И. Яровая (внс ЛФАВ), к.х.н. А.Д. Рогачев (снс, ЛФАВ), д.б.н. Д.С. Баев (снс, ЛФИ), д.б.н., проф. Т.Г. Толстикова (завлаб ЛФИ) и д.х.н., проф., чл.-корр РАН, зав отдеом ОМХ Н.Ф. Салахутдинов.

Biostability, in vivo antiviral activity against respiratory syncytial virus, and pharmacokinetic profiles of (−)-borneol esters

Anastasiya S. Sokolova,  Alina A. Okhina, Anna A. Shtro, Artem M. Klabukov, Anastasia V. Galochkina, Yulia V. Nikolaeva , Galina D. Petukhova, Olga I. Yarovaya, Artem D. Rogachev, Dmitriy S. Baev, Alina V. Fatyanova , Tatyana G. Tolstikova and Nariman F. Salakhutdinov

European Journal of Pharmacology, Volume 996, 177567

Published: 5 June 2025,

 DOI: 10.1016/j.ejphar.2025.177567

Abstract

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections, particularly in vulnerable populations such as infants and the elderly. In this study, we evaluated the metabolic stability, in vivo antiviral activity, and pharmacokinetic profiles of (−)-borneol esters, which were identified as potent RSV inhibitors through screening of a compound library. Two hit compounds, ST-2 and AS-645, caused a reduction in viral titers in RSV-infected mice. Intranasal administration of ST-2 proved more effective than oral one and showed enhanced antiviral activity and improved pharmacokinetic properties. Additionally, ST-2 manifested superior metabolic stability in human blood compared to murine and rat blood, suggesting that carboxylesterase activity is a key factor in the hydrolysis resistance. Given that carboxylesterase activity is higher in mouse blood than in human blood, this difference likely contributes to the observed stability of ST-2 in human blood. Molecular modeling confirmed the role of carboxylesterase in the hydrolysis of (−)-borneol esters. These findings suggest that ST-2 has potential for further development of drugs for RSV and other viral infections.

Keywords: 

(−)-borneol ester, Respiratory syncytial virus inhibitor, In vivo antiviral activity, Pharmacokinetics, Metabolic stability

 

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