Biostability, In Vivo Antiviral Activity against Respiratory Syncytial Virus, and Pharmacokinetic Profiles of (-)-Borneol Esters | Sciact - CRIS-система Института катализа

Biostability, In Vivo Antiviral Activity against Respiratory Syncytial Virus, and Pharmacokinetic Profiles of (-)-Borneol Esters Научная публикация

Журнал

European Journal of Pharmacology
ISSN: 1879-0712

Вых. Данные

Год: 2025, Том: 996, Номер статьи : 177567, Страниц : 10 DOI: 10.1016/j.ejphar.2025.177567

Ключевые слова

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

Авторы

Sokolova Anastasiya S. ¹ , Okhina Alina A. ^1,4 , Shtro Anna A. ² , Klabukov Artem M. ² , Galochkina Anastasia V. ² , Nikolaeva Yulia V. ² , Petukhova Galina D. ² , Yarovaya Olga I. ¹ , Rogachev Artem D. ^1,4 , Baev Dmitriy S. ^1,3 , Fatyanova Alina V. ⁴ , Tolstikova Tatyana G. ¹ , Salakhutdinov Nariman F. ¹

Организации

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Akad. Lavrentiev Ave. 9, Novosibirsk 630090, Russian Federation
2	Smorodintsev Research Institute of Influenza, Prof. Popov Str. 15/17, Saint Petersburg 197376, Russian Federation
3	SRF SKIF, Koltsovo, Novosibirsk region 630559, Russian Federation
4	Novosibirsk State University, Pirogova Str. 1, Novosibirsk 630090, Russian Federation.

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.

Sokolova A.S. , Okhina A.A. , Shtro A.A. , Klabukov A.M. , Galochkina A.V. , Nikolaeva Y.V. , Petukhova G.D. , Yarovaya O.I. , Rogachev A.D. , Baev D.S. , Fatyanova A.V. , Tolstikova T.G. , Salakhutdinov N.F.
Biostability, In Vivo Antiviral Activity against Respiratory Syncytial Virus, and Pharmacokinetic Profiles of (-)-Borneol Esters
European Journal of Pharmacology. 2025. V.996. 177567 :1-10. DOI: 10.1016/j.ejphar.2025.177567 Scopus OpenAlex СКИФ ID

Поступила в редакцию:	10 янв. 2025 г.
Принята к публикации:	31 мар. 2025 г.
Опубликована online:	4 апр. 2025 г.
Опубликована в печати:	5 июн. 2025 г.

Scopus:	2-s2.0-105001990450
OpenAlex:	W4409199395
СКИФ ID:	3821

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