Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process

Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process Full article

Journal

European Journal of Medicinal Chemistry
ISSN: 0223-5234 , E-ISSN: 1768-3254

Output data

Year: 2020, Volume: 207, Article number : 112726, Pages count : DOI: 10.1016/j.ejmech.2020.112726

Tags

Borneol; Camphor; Ebola virus; Glycoprotein; Marburg virus; Mutagenesis study

Authors

Sokolova A.S. ¹ , Yarovaya O.I. ^1,2 , Zybkina A.V. ³ , Mordvinova E.D. ^1,3 , Shcherbakova N.S. ³ , Zaykovskaya A.V. ³ , Baev D.S. ¹ , Tolstikova T.G. ^1,2 , Shcherbakov D.N. ³ , Pyankov O.V. ³ , Maksyutov R.A. ³ , Salakhutdinov N.F. ¹

Affiliations

1	(Scopus) N.N.Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrent'ev Av., 9, Novosibirsk, 630090, Russian Federation
2	(Scopus) Novosibirsk State University, Pirogova St., 1, Novosibirsk, 630090, Russian Federation
3	(Scopus) State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, Novosibirsk Region, Koltsovo, 630559, Russian Federation

In this study, we screened a large library of (+)-camphor and (−)-borneol derivatives to assess their filovirus entry inhibition activities using pseudotype systems. Structure-activity relationship studies revealed several compounds exhibiting submicromolar IC50 values. These compounds were evaluated for their effect against natural Ebola virus (EBOV) and Marburg virus. Compound 3b (As-358) exhibited the good antiviral potency (IC50 = 3.7 μM, SI = 118) against Marburg virus, while the hydrochloride salt of this compound 3b·HCl had a strong inhibitory effect against Ebola virus (IC50 = 9.1 μM, SI = 31) and good in vivo safety (LD50 > 1000 mg/kg). The results of molecular docking and in vitro mutagenesis analyses suggest that the synthesized compounds bind to the active binding site of EBOV glycoprotein similar to the known inhibitor toremifene. © 2020 Elsevier Masson SAS

Sokolova A.S. , Yarovaya O.I. , Zybkina A.V. , Mordvinova E.D. , Shcherbakova N.S. , Zaykovskaya A.V. , Baev D.S. , Tolstikova T.G. , Shcherbakov D.N. , Pyankov O.V. , Maksyutov R.A. , Salakhutdinov N.F.
Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process
European Journal of Medicinal Chemistry. 2020. V.207. 112726 . DOI: 10.1016/j.ejmech.2020.112726 WOS Scopus РИНЦ

Published print:

Dec 1, 2020

Web of science	WOS:000591227400017
Scopus	2-s2.0-85090247641
Elibrary	45316996
OpenAlex	W3080636360