Multi-Step In Silico Discovery of Natural Drugs against COVID-19 Targeting Main Protease

In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (Mpro) inhibitors among 310 naturally originated antiviral compounds. This was pe...

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Published in:International journal of molecular sciences 2022-06, Vol.23 (13), p.6912
Main Authors: Elkaeed, Eslam B., Youssef, Fadia S., Eissa, Ibrahim H., Elkady, Hazem, Alsfouk, Aisha A., Ashour, Mohamed L., El Hassab, Mahmoud A., Abou-Seri, Sahar M., Metwaly, Ahmed M.
Format: Article
Language:English
Subjects:
Antiviral agents
Binding
Coronaviruses
COVID-19
Crystallization
Disease transmission
Drug delivery
Drug discovery
Hydrogen bonds
Ligands
Molecular docking
Molecular dynamics
Molecular structure
Protease
Protease inhibitors
Proteinase inhibitors
Severe acute respiratory syndrome coronavirus 2
Software
Toxicity
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Summary:In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (Mpro) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, a molecular structure similarity study was done with PRD_002214, the co-crystallized ligand of Mpro (PDB ID: 6LU7), and favored thirty compounds. Subsequently, the fingerprint study performed with respect to PRD_002214 resulted in the election of sixteen compounds (7, 128, 130, 156, 157, 158, 180, 184, 203, 204, 210, 237, 264, 276, 277, and 278). Then, results of molecular docking versus Mpro PDB ID: 6LU7 favored eight compounds (128, 130, 156, 180, 184, 203, 204, and 278) based on their binding affinities. Then, in silico toxicity studies were performed for the promising compounds and revealed that all of them have good toxicity profiles. Finally, molecular dynamic (MD) simulation experiments were carried out for compounds 130, 184, and 278, which exhibited the best binding modes against Mpro. MD tests revealed that luteoside C (130) has the greatest potential to inhibit SARS-CoV-2 main protease.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23136912