1. In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (Mpro) Inhibitors
- Author
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Ibrahim, Mahmoud A. A., Abdelrahman, Alaa H. M., Mohamed, Tarik A., Atia, Mohamed A. M., Al-Hammady, Montaser A. M., Abdeljawaad, Khlood A. A., Elkady, Eman M., Moustafa, Mahmoud F., Alrumaihi, Faris, Allemailem, Khaled S., El-Seedi, Hesham R., Paré, Paul W., Efferth, Thomas, and Hegazy, Mohamed-Elamir F.
- Subjects
Binding Sites ,SARS-CoV-2 ,Terpenes ,COVID-19 ,marine natural products ,Hydrogen Bonding ,molecular docking ,Molecular Dynamics Simulation ,Invertebrates ,Lopinavir ,Article ,molecular dynamics ,COVID-19 Drug Treatment ,drug discovery ,lcsh:QD241-441 ,Molecular Docking Simulation ,Viral Matrix Proteins ,SARS-CoV-2 main protease ,lcsh:Organic chemistry ,Animals ,Humans ,Thermodynamics ,Protease Inhibitors ,virtual drug screening ,Protein Binding - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (Mpro) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of in silico analyses, six terpenes demonstrated high potency as Mpro inhibitors with ΔGbinding ≤ −40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 Mpro than lopinavir over 100 ns with ΔGbinding values of −51.9 vs. −33.6 kcal/mol, respectively. Protein–protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components BCL2L1, IL2, and PRKC. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target–function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further in vitro and in vivo testing.
- Published
- 2021