Exploring the efficacy of natural compounds against SARS-CoV-2: A synergistic approach integrating molecular docking and dynamic simulation

Main Article Content

Nabila Aoumeur
https://orcid.org/0000-0002-6069-5639
Mebarka Ouassaf
https://orcid.org/0000-0002-0292-0949
Salah Belaidi
https://orcid.org/0000-0002-6949-4518
Noureddine Tchouar
Lotfi Bouragaa
https://orcid.org/0009-0005-4235-6077
Imane Yamari
https://orcid.org/0000-0002-8406-8533
Samir Chtita
https://orcid.org/0000-0003-2344-5101
Leena Sinha

Abstract

The primary aim of the current investigation is to contribute significantly to SARS-CoV-2 research by identifying potential lead compounds for clinical applications, with a specific focus on inhibitors targeting the main protease (Mpro). In this research, molecular docking analysis was conducted using the software molecular operating environmental (MOE) to evaluate the potential of bioactive compounds sourced from medicinal plants as inhibitors of SARS-CoV-2 Mpro. Among 118 natural compounds with anti-HIV characteristics, the top seven candidates (h3, h84, h85, h87, h90, h108, and h110), were identified based on their superior binding energies with comparison to the reference ligand N3. These selected compounds exhibited binding affinities of -33.996, -35.336, -32.615, -32.154, -33.452, -31.903, and -40.360 kJ mol-1, respectively. To further refine our shortlist of potential candidates for human application, we examined the drug-likeness, and the pharmaceutical attributes of these compounds using the SwissADME web server. Among them, only two compounds, namely h85 and h87, demonstrated favorable pharmacological properties suitable for human administration. These two compounds were subsequently shortlisted for further investigation. To explore the conformational stability of ligands within the Mproactive site, we performed molecular dynamics (MD) simulations. These simulations showed reliable and steady trajectories, supported by analyses of root-mean-square-fluctuation 'RMSF' and root-mean-square deviation 'RMSD'. These findings and favorable molecular properties and interaction profiles suggest that these two lead compounds may be promising SARS-CoV-2 therapeutic candidates. They present exciting starting points for further drug design.

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How to Cite
[1]
N. Aoumeur, “Exploring the efficacy of natural compounds against SARS-CoV-2: A synergistic approach integrating molecular docking and dynamic simulation”, J. Serb. Chem. Soc., Mar. 2024.
Section
Theoretical Chemistry

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