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

Результат исследования: Научные публикации в периодических изданияхстатья

Аннотация

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.

Язык оригиналаанглийский
Номер статьи112726
ЖурналEuropean Journal of Medicinal Chemistry
Том207
Ранняя дата в режиме онлайн20 авг 2020
DOI
СостояниеЭлектронная публикация перед печатью - 20 авг 2020

Fingerprint Подробные сведения о темах исследования «Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process». Вместе они формируют уникальный семантический отпечаток (fingerprint).

  • Цитировать

    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. (2020). Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process. European Journal of Medicinal Chemistry, 207, [112726]. https://doi.org/10.1016/j.ejmech.2020.112726