Microbial natural products as potential inhibitors of SARS-CoV-2 main protease (Mpro)

Ahmed M. Sayed, Hani A. Alhadrami, Ahmed O. El-Gendy, Yara I. Shamikh, Lassaad Belbahri, Hossam M. Hassan, Usama Ramadan Abdelmohsen*, Mostafa E. Rateb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)
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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 (>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 Mpro 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.

Original languageEnglish
Article number970
Number of pages17
Issue number7
Publication statusPublished - 29 Jul 2020


  • Covid-19
  • docking
  • Mpro
  • microbial natural products
  • molecular dynamic simulation
  • SARS-CoV-2


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