Back to Search
Start Over
Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition.
- Source :
- Marine Drugs; Jul2021, Vol. 19 Issue 7, p391-391, 1p
- Publication Year :
- 2021
-
Abstract
- The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (M<superscript>pro</superscript>) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target M<superscript>pro</superscript>, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 M<superscript>pro</superscript> inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as M<superscript>pro</superscript> inhibitors with ΔG<subscript>binding</subscript> < −33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against M<superscript>pro</superscript> than darunavir with ΔG<subscript>binding</subscript> values of −43.8 and −34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16603397
- Volume :
- 19
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Marine Drugs
- Publication Type :
- Academic Journal
- Accession number :
- 151587249
- Full Text :
- https://doi.org/10.3390/md19070391