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 M pro inhibitors with Δ G binding ≤ −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 M pro than lopinavir over 100 ns with Δ G binding 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.
【저자키워드】 Drug discovery, molecular docking, Virtual drug screening, molecular dynamics, SARS-CoV-2 main protease, marine natural products, 【초록키워드】 COVID-19, SARS-CoV-2, coronavirus, Diseases, COVID-19 pandemic, cytokine, protease, in vitro, in silico, inhibitors, binding affinity, binding energy, Protease inhibitor, infections, stability, death, molecular, in vivo, inhibitor, Human immunodeficiency virus, enrichment analysis, interactions, metabolite, binding, Signaling, Interaction, acute respiratory syndrome, biochemical, M pro, treat, component, antiviral medication, BCL2L1, ecosystem, greater, identify, performed, reported, addition, screened, demonstrated, analyses, IL2, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, M pro, invertebrate, terpene,