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Updated: Oct 25, 2025
Assays for the Identification of Novel Antivirals against Bluetongue Virus
Published on: October 11, 2013
Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease
Mahmoud A A Ibrahim1, Alaa H M Abdelrahman1, Mohamed A M Atia2
1Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt.
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 (Mpro) 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 Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro 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 Mpro inhibitors with ΔGbinding < -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 Mpro than darunavir with ΔGbinding 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.
Insights
Researchers identified bislatumlide A from soft corals as a potent inhibitor of SARS-CoV-2 main protease (Mpro). This natural compound shows higher binding affinity than darunavir, suggesting potential as a novel COVID-19 antiviral drug.
Area of Science:
- Natural Product Chemistry
- Computational Drug Discovery
- Virology
Background:
- The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths globally.
- Effective antiviral therapies for COVID-19 are lacking, highlighting the need for new drug candidates.
- The SARS-CoV-2 main protease (Mpro) is crucial for viral replication and represents a key drug target.
Purpose of the Study:
- To identify potential SARS-CoV-2 Mpro inhibitors from the soft coral genus Sarcophyton.
- To evaluate the binding affinity and drug-likeness of promising natural compounds using computational methods.
- To investigate the potential therapeutic mechanisms of the lead compound against SARS-CoV-2.
Main Methods:
- Screening of over 360 Sarcophyton metabolites using molecular docking.
- In-depth analysis of top candidates via molecular dynamics (MD) simulations and MM-GBSA binding energy calculations.
- Comparison of binding affinity with darunavir, assessment of drug-likeness, and pathway enrichment analysis.
Main Results:
- Five cembranoid diterpenes showed significant Mpro inhibitory potential with binding affinities below -33.0 kcal/mol.
- Bislatumlide A (340) exhibited superior binding affinity (-43.8 kcal/mol) compared to darunavir (-34.8 kcal/mol) over 100 ns MD simulations.
- Bislatumlide A demonstrated favorable drug-likeness, identified interactions with key genes (ACE, MAPK14, ESR1), and potential to modulate the p38 MAPK pathway.
Conclusions:
- Bislatumlide A is a highly promising natural compound for targeting SARS-CoV-2 Mpro.
- Computational analyses suggest bislatumlide A possesses strong antiviral potential and favorable pharmacokinetic properties.
- Further in vitro and in vivo studies are warranted to validate bislatumlide A as a therapeutic agent against COVID-19.
