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In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M pro) Inhibitors.
- Source :
- Molecules; Apr2021, Vol. 26 Issue 7, p2082, 1p
- Publication Year :
- 2021
-
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 (M<superscript>pro</superscript>) 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<superscript>pro</superscript> inhibitors with ΔG<subscript>binding</subscript> ≤ −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<superscript>pro</superscript> than lopinavir over 100 ns with ΔG<subscript>binding</subscript> 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- TERPENES
SARS-CoV-2
COVID-19 pandemic
COVID-19
HIV
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 26
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- 149715836
- Full Text :
- https://doi.org/10.3390/molecules26072082