Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus | Sciact - CRIS-system of Boreskov Institute of Catalysis

Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus Full article

Journal

International Journal of Molecular Sciences
ISSN: 1422-0067 , E-ISSN: 1661-6596

Output data

Year: 2023, Volume: 24, Number: 16, Article number : 12933, Pages count : 16 DOI: 10.3390/ijms241612933

Tags

coumarin; antiviral activity; cytotoxicity; respiratory syncytial virus

Authors

Shtro Anna A. ¹ , Klabukov Artem M. ¹ , Garshinina Anzhelika V. ¹ , Galochkina Anastasia V. ¹ , Nikolaeva Yulia V. ¹ , Khomenko Tatyana M. ² , Bobkov Danila E. ^3,1 , Lozhkov Aleksey A. ¹ , Sivak Konstantin V. ¹ , Yakovlev Kirill S. ¹ , Komissarov Andrey B. ¹ , Borisevich Sophia S. ⁴ , Volcho Konstantin P. ² , Salakhutdinov Nariman F. ²

Affiliations

1	Smorodintsev Research Institute of Influenza, Professora Popova str, 15/17, 197376 St. Petersburg, Russia
2	Vorozhtsov Novosibirsk Institute of Organic Chemistry, Acad. Lavrentyev av. 9, 630090 Novosibirsk, Russia
3	Institute of Cytology Russian Academy of Science, Tikhoretsky av., 4, 194064 St. Petersburg, Russia
4	Ufa Chemistry Institute of the Ufa Federal Research Center, 71 Octyabrya pr., 450054 Ufa, Russia

Respiratory syncytial virus (RSV) is known to cause annual epidemics of respiratory infections; however, the lack of specific treatment options for this disease poses a challenge. In light of this, there has been a concerted effort to identify small molecules that can effectively combat RSV. This article focuses on the mechanism of action of compound K142, which was identified as a primary screening leader in the earlier stages of the project. The research conducted demonstrates that K142 significantly reduces the intensity of virus penetration into the cells, as well as the formation of syncytia from infected cells. These findings show that the compound’s interaction with the surface proteins of RSV is a key factor in its antiviral activity. Furthermore, pharmacological modeling supports that K142 effectively interacts with the F-protein. However, in vivo studies have shown only weak antiviral activity against RSV infection, with a slight decrease in viral load observed in lung tissues. As a result, there is a need to enhance the bioavailability or antiviral properties of this compound. Based on these findings, we hypothesize that further modifications of the compound under study could potentially increase its antiviral activity.

Shtro A.A. , Klabukov A.M. , Garshinina A.V. , Galochkina A.V. , Nikolaeva Y.V. , Khomenko T.M. , Bobkov D.E. , Lozhkov A.A. , Sivak K.V. , Yakovlev K.S. , Komissarov A.B. , Borisevich S.S. , Volcho K.P. , Salakhutdinov N.F.
Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus
International Journal of Molecular Sciences. 2023. V.24. N16. 12933 :1-16. DOI: 10.3390/ijms241612933 WOS Scopus ANCAN PMID OpenAlex

Submitted:	Jul 10, 2023
Accepted:	Aug 15, 2023
Published print:	Aug 18, 2023
Published online:	Aug 18, 2023

Web of science:	WOS:001057429300001
Scopus:	2-s2.0-85168727368
Chemical Abstracts:	2023:1834877
Chemical Abstracts (print):	184:162788
PMID:	37629115
OpenAlex:	W4385982005

DB	Citing
OpenAlex	4
Web of science	3
Scopus	4