Molecular Docking and Dynamics Simulation Study of Hyrtios erectus Isolated Scalarane Sesterterpenes as Potential SARS-CoV-2 Dual Target Inhibitors

Presently, the world is under the toll of pandemic coronavirus disease-2019 (COVID-19) outbreak caused by SARS-CoV-2. Lack of effective and safe therapeutics has stressed the scientific community for developing novel therapeutics capable of alleviating and stopping this pandemic. Within the presente...

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Published in:Biology (Basel, Switzerland) Switzerland), 2021-05, Vol.10 (5), p.389
Main Authors: Elhady, Sameh S., Abdelhameed, Reda F. A., Malatani, Rania T., Alahdal, Abdulrahman M., Bogari, Hanin A., Almalki, Ahmad J., Mohammad, Khadijah A., Ahmed, Safwat A., Khedr, Amgad I. M., Darwish, Khaled M.
Format: Article
Language:English
Subjects:
Antiviral agents
Binding sites
Chromatography
Coronaviruses
COVID-19
Drug development
Drugs
Enzymes
FDA approval
Hyrtios
Hyrtios erectus
Ligands
Lopinavir
main protease
Metabolites
Nsp15 endoribonuclease
Pandemics
Proteinase
Proteins
Red Sea
scalarane sesterterpenes
Severe acute respiratory syndrome coronavirus 2
Simulation
Therapeutic applications
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Summary:Presently, the world is under the toll of pandemic coronavirus disease-2019 (COVID-19) outbreak caused by SARS-CoV-2. Lack of effective and safe therapeutics has stressed the scientific community for developing novel therapeutics capable of alleviating and stopping this pandemic. Within the presented study, molecular docking, ADME properties and all-atom molecular dynamic (MD) simulation, along with two standard antiviral agents (lopinavir and benzopurpurin-4B), were applied to investigate 15 scalaranes sesterterpenes natural compounds, purified from the Red Sea marine sponge Hyrtios erectus, as potential COVID-19 dual-target inhibitors. Following multi-step docking within COVID-19 main protease and Nsp15 endoribonuclease cavities, nine promising drug-like compounds exhibited higher docking scores as well as better interactions with the target’s crucial residues than those of reference ligands. Compounds 2, 6, 11, and 15, were predicted to simultaneously subdue the activity of the two COVID-19 targets. Dynamics behavior of the best-docked molecules, compounds 15 and 6, within COVID-19 target pockets showed substantial stability of ligand-protein complexes as presented via several MD simulation parameters. Furthermore, calculated free-binding energies from MD simulation illustrated significant ligand’s binding affinity towards respective target pockets. All provided findings supported the utility of scalarane-based sesterterpenes, particularly compounds 15 and 6, as promising lead candidates guiding the development of effective therapeutics against SARS-CoV-2.
ISSN:2079-7737
2079-7737
DOI:10.3390/biology10050389