@article{Sayed_A-2020_10745,
title = {Microbial natural products as potential inhibitors of SARS-CoV-2 main protease (Mpro)},
author = {Sayed, A. and Alhadrami, H. and El-Gendy, A. and Shamikh, Y. and Belbahri, L. and Hassan, H. and Abdelmohsen, U. and Rateb, M.},
month = {jul},
year = {2020},
abstract = {The main protease (Mpro) of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subjected to hyphenated pharmacophoric-based and structural-based virtual screenings using a library of microbial natural products (&gt;24,000 compounds). Subsequent filtering of the resulted hits according to the Lipinski’s rules was applied to select only the drug-like molecules. Top-scoring hits were further filtered out depending on their ability to show constant good binding affinities towards the molecular dynamic simulation (MDS)-derived enzyme’s conformers. Final MDS experiments were performed on the ligand–protein complexes (compounds 1–12, Table S1) to verify their binding modes and calculate their binding free energy. Consequently, a final selection of six compounds (1–6) was proposed to possess high potential as anti-SARS-CoV-2 drug candidates. Our study provides insight into the role of the Mprostructural flexibility during interactions with the possible inhibitors and sheds light on the structure-based design of anti-coronavirus disease 2019 (COVID-19) therapeutics targeting SARS-CoV-2.},
volume = {8},
issue = {7},
journal = {Microorganisms},
publisher = {MDPI},
url = {https://doi.org/10.3390/microorganisms8070970},
}
