| Literature DB >> 32905862 |
Anastasiya S Sokolova1, Olga I Yarovaya2, Anastasiya V Zybkina3, Ekaterina D Mordvinova4, Nadezhda S Shcherbakova3, Anna V Zaykovskaya3, Dmitriy S Baev5, Tatyana G Tolstikova2, Dmitriy N Shcherbakov3, Oleg V Pyankov3, Rinat A Maksyutov3, Nariman F Salakhutdinov5.
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.Entities:
Keywords: Borneol; Camphor; Ebola virus; Glycoprotein; Marburg virus; Mutagenesis study
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Year: 2020 PMID： 32905862 DOI： 10.1016/j.ejmech.2020.112726
Source DB: PubMed Journal: Eur J Med Chem ISSN： 0223-5234 Impact factor: 6.514