Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses
2022
Olga I. Yarovaya | Dmitriy N. Shcherbakov | Sophia S. Borisevich | Anastasiya S. Sokolova | Maxim A. Gureev | Edward M. Khamitov | Nadezda B. Rudometova | Anastasiya V. Zybkina | Ekaterina D. Mordvinova | Anna V. Zaykovskaya | Artem D. Rogachev | Oleg V. Pyankov | Rinat A. Maksyutov | Nariman F. Salakhutdinov
In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study the inhibition of the re-receptor-binding domain of protein S. For the compounds that showed activity on the pseudoviral system, a study using three strains of the infectious SARS-CoV-2 virus was carried out. As a result, two leader compounds were found that showed activity on the Wuhan, Delta, and Omicron strains. Based on the biological results, we searched for the potential binding site of the leader compounds using molecular dynamics and molecular docking methods. We suggested that the compounds can bind in conserved regions of the central helices and/or heptad repeats of glycoprotein S of SARS-CoV-2 viruses.
显示更多 [+] 显示较少 [-]