Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses Full article

Journal

Molecules
, E-ISSN: 1420-3049

Output data

Year: 2021, Volume: 26, Number: 8, Article number : 2235, Pages count : DOI: 10.3390/molecules26082235

Tags

camphen; antiviral agent; surface protein; pseudotype viruses; molecular docking

Authors

Sokolova Anastasiya S. ¹ , Putilova Valentina P. ¹ , Yarovaya Olga I. ¹ , Zybkina Anastasiya V. ² , Mordvinova Ekaterina D. ^1,2 , Zaykovskaya Anna V. ² , Shcherbakov Dmitriy N. ² , Orshanskaya Iana R. ³ , Sinegubova Ekaterina O. ³ , Esaulkova Iana L. ³ , Borisevich Sophia S. ⁴ , Bormotov Nikolay I. ² , Shishkina Larisa N. ² , Zarubaev Vladimir V. ³ , Pyankov Oleg V. ² , Maksyutov Rinat A. ² , Salakhutdinov Nariman F. ¹

Affiliations

1	(Данные Web of science) RAS, NN Vorozhtsov Novosibirsk Inst Organ Chem SB, Lavrentev Av 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Rospotrebnadzor, State Res Ctr Virol & Biotechnol VECTOR, Novosibirsk 630559, Russia
3	(Данные Web of science) Pasteur Inst Epidemiol & Microbiol, 14 Mira Str, St Petersburg 197101, Russia
4	(Данные Web of science) Ufa Fed Res Ctr, Ufa Inst Chem, Lab Chem Phys, 71 Pr Oktyabrya, Ufa 450078, Russia

To date, the 'one bug-one drug' approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC50 = 45.3 mu M), Ebola pseudotype viruses (IC50 = 0.12 mu M), and authentic EBOV (IC50 = 18.3 mu M), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC50 = 9.1 mu M). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.

Sokolova A.S. , Putilova V.P. , Yarovaya O.I. , Zybkina A.V. , Mordvinova E.D. , Zaykovskaya A.V. , Shcherbakov D.N. , Orshanskaya I.R. , Sinegubova E.O. , Esaulkova I.L. , Borisevich S.S. , Bormotov N.I. , Shishkina L.N. , Zarubaev V.V. , Pyankov O.V. , Maksyutov R.A. , Salakhutdinov N.F.
Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

Molecules. 2021. V.26. N8. 2235 . DOI: 10.3390/molecules26082235 WOS Scopus РИНЦ

Full text from publisher

Published online:

Apr 13, 2021

Web of science	WOS:000644584800001
Scopus	2-s2.0-85105056890
Elibrary	46031364
OpenAlex	W3156337027