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

Anastasiya S. Sokolova, Olga I. Yarovaya, Anastasiya V. Zybkina, Ekaterina D. Mordvinova, Nadezhda S. Shcherbakova, Anna V. Zaykovskaya, Dmitriy S. Baev, Tatyana G. Tolstikova, Dmitriy N. Shcherbakov, Oleg V. Pyankov, Rinat A. Maksyutov, Nariman F. Salakhutdinov

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number112726
Number of pages17
JournalEuropean Journal of Medicinal Chemistry
Volume207
Early online date20 Aug 2020
DOIs
Publication statusPublished - 1 Dec 2020

Keywords

  • Borneol
  • Camphor
  • Ebola virus
  • Glycoprotein
  • Marburg virus
  • Mutagenesis study
  • IN-VITRO
  • DRUG DISCOVERY
  • BORNEOL DERIVATIVES
  • IDENTIFICATION
  • EBOLA-VIRUS

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