In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M pro) Inhibitors.
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Ibrahim MAA, Abdelrahman AHM, Mohamed TA, Atia MAM, Al-Hammady MAM, Abdeljawaad KAA, Elkady EM, Moustafa MF, Alrumaihi F, Allemailem KS, El-Seedi HR, Paré PW, Efferth T, Hegazy MF
Molecules 26 (7) - [2021-04-05; online 2021-04-05]
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 (M pro) 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.
PubMed 33916461
DOI 10.3390/molecules26072082
Crossref 10.3390/molecules26072082
pii: molecules26072082
pmc: PMC8038614
NCBI: NC_045512.2 Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome