In silico drug discovery of major metabolites from spices as SARS-CoV-2 main protease inhibitors

Mahmoud A.A. Ibrahim, Alaa H.M. Abdelrahman, Taha A. Hussien, Esraa A.A. Badr, Tarik A. Mohamed, Hesham R. El-Seedi, Paul W. Pare, Thomas Efferth, Mohamed Elamir F. Hegazy

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (Mpro), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcumin as Mpro inhibitors with binding energies of −9.7 and −9.2 kcal/mol, respectively. Binding mode analysis demonstrated the ability of salvianolic acid A and curcumin to form nine and six hydrogen bonds, respectively with amino acids proximal to Mpro's active site. Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). Molecular mechanics-generalized Born surface area energy calculations revealed greater salvianolic acid A affinity for the enzyme over curcumin and lopinavir with energies of −44.8, −34.2 and −34.8 kcal/mol, respectively. Using a STRING database, protein-protein interactions were identified for salvianolic acid A included the biochemical signaling genes ACE, MAPK14 and ESR1; and for curcumin, EGFR and TNF. This study establishes salvianolic acid A as an in silico natural product inhibitor against the SARS-CoV-2 main protease and provides a promising inhibitor lead for in vitro enzyme testing.

Original languageEnglish
Article number104046
JournalComputers in Biology and Medicine
Volume126
DOIs
StatePublished - Nov 2020

Keywords

  • Molecular docking
  • Molecular dynamics
  • SARS-CoV-2 main protease
  • Secondary metabolites
  • Spices

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