Discovery of N-Containing (-)-Borneol Esters as Respiratory Syncytial Virus Fusion Inhibitors | Sciact - CRIS-система Института катализа

Discovery of N-Containing (-)-Borneol Esters as Respiratory Syncytial Virus Fusion Inhibitors Научная публикация

Журнал

Pharmaceuticals
ISSN: 1424-8247

Вых. Данные

Год: 2022, Том: 15, Номер: 11, Номер статьи : 1390, Страниц : 20 DOI: 10.3390/ph15111390

Ключевые слова

(-)-borneol; virus entry inhibitor; surface F protein; molecular docking

Авторы

Sokolova Anastasiya S. ¹ , Yarovaya Olga I. ¹ , Kuzminykh Lana V. ¹ , Shtro Anna A. ² , Klabukov Artem M. ² , Galochkina Anastasia V. ² , Nikolaeva Yulia V. ² , Petukhova Galina D. ² , Borisevich Sophia S. ³ , Khamitov Edward M. ³ , Salakhutdinov Nariman F. ¹

Организации

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrentiev Ave., 9, 630090 Novosibirsk, Russia
2	Smorodintsev Research Institute of Influenza, Prof. Popov St., 15/17, 197376 Saint-Petersburg, Russia
3	Laboratory of Physical Chemistry, Chemistry Institute of the Ufa Federal Research Center, Octyabrya Pr., 71, 450054 Ufa, Russia

Respiratory syncytial virus (RSV) causes acute respiratory infections, thus, posing a serious threat to the health of infants, children, and elderly people. In this study, we have discovered a series of potent RSV entry inhibitors with the (-)-borneol scaffold. The active compounds 3b, 5a, 5c, 7b, 9c, 10b, 10c, and 14b were found to exhibit activity against RSV A strain A2 in HEp-2 cells. The most active substances, 3b (IC50 = 8.9 μM, SI = 111) and 5a (IC50 = 5.0 μM, SI = 83), displayed more potency than the known antiviral agent Ribavirin (IC50 = 80.0 μM, SI = 50). Time-of-addition assay and temperature shift studies demonstrated that compounds 3b, 5a, and 6b inhibited RSV entry, probably by interacting with the viral F protein that mediated membrane fusion, while they neither bound to G protein nor inhibited RSV attachment to the target cells. Appling procedures of molecular modeling and molecular dynamics, the binding mode of compounds 3b and 5a was proposed. Taken together, the results of this study suggest (-)-borneol esters to be promising lead compounds for developing new anti-RSV agents.

Sokolova A.S. , Yarovaya O.I. , Kuzminykh L.V. , Shtro A.A. , Klabukov A.M. , Galochkina A.V. , Nikolaeva Y.V. , Petukhova G.D. , Borisevich S.S. , Khamitov E.M. , Salakhutdinov N.F.
Discovery of N-Containing (-)-Borneol Esters as Respiratory Syncytial Virus Fusion Inhibitors
Pharmaceuticals. 2022. V.15. N11. 1390 :1-20. DOI: 10.3390/ph15111390 WOS Scopus CAPlus PMID OpenAlex

Поступила в редакцию:	25 сент. 2022 г.
Принята к публикации:	8 нояб. 2022 г.
Опубликована в печати:	8 нояб. 2022 г.
Опубликована online:	11 нояб. 2022 г.

Web of science:	WOS:000895378600001
Scopus:	2-s2.0-85149216416
Chemical Abstracts:	2022:3132855
PMID (PubMed):	36422520
OpenAlex:	W4308973284

БД	Цитирований
OpenAlex	14
Web of science	11
Scopus	13