Microbial Natural Products as Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro)

Microorganisms

Hani A. Alhadrami¹  Yara I. Shamikh²  Ahmed O. El-Gendy³  Hossam M. Hassan⁴  Usama Ramadan Abdelmohsen⁵  Ahmed M. Sayed⁶  Lassaad Belbahri⁷  Mostafa E. Rateb⁸ 

[1] Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia;Department of Microbiology & Immunology, Nahda University, Beni-Suef 62513, Egypt;Department of Microbiology, Faculty of Pharmacy, Beni-Suef University, 62514Beni-Suef, Egypt;Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, 62514 Beni-Suef, Egypt;Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt;Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, 62513 Beni-Suef, Egypt;Laboratory of Soil Biology, Department of Biology, University of Neuchatel, 2000 Neuchatel, Switzerland;School of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK;

关键词: SARS-CoV-2;    Covid-19;    Mpro;    microbial natural products;    docking;    molecular dynamic simulation;   

DOI  :  10.3390/microorganisms8070970

来源: DOAJ

【 摘 要 】

The main protease (M^pro) 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 (>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 M^pro structural 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.

【 授权许可】

Unknown