Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein
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Published:2023-11-02
Issue:21
Volume:24
Page:15894
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Moschovou Kalliopi1, Antoniou Maria23, Chontzopoulou Eleni1, Papavasileiou Konstantinos D.23ORCID, Melagraki Georgia4, Afantitis Antreas23ORCID, Mavromoustakos Thomas1ORCID
Affiliation:
1. Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece 2. Department of ChemoInformatics, NovaMechanics Ltd., 1046 Nicosia, Cyprus 3. Department of Chemoinformatics, NovaMechanics MIKE, 18536 Piraeus, Greece 4. Division of Physical Sciences & Applications, Hellenic Military Academy, 16672 Vari, Greece
Abstract
In this in silico study, we conducted an in-depth exploration of the potential of natural products and antihypertensive molecules that could serve as inhibitors targeting the key proteins of the SARS-CoV-2 virus: the main protease (Mpro) and the spike (S) protein. By utilizing Induced Fit Docking (IFD), we assessed the binding affinities of the molecules under study to these crucial viral components. To further comprehend the stability and molecular interactions of the “protein-ligand” complexes that derived from docking studies, we performed molecular dynamics (MD) simulations, shedding light on the molecular basis of potential drug candidates for COVID-19 treatment. Moreover, we employed Molecular Mechanics Generalized Born Surface Area (MM-GBSA) calculations on all “protein-ligand” complexes, underscoring the robust binding capabilities of rosmarinic acid, curcumin, and quercetin against Mpro, and salvianolic acid b, rosmarinic acid, and quercetin toward the S protein. Furthermore, in order to expand our search for potent inhibitors, we conducted a structure similarity analysis, using the Enalos Suite, based on the molecules that indicated the most favored results in the in silico studies. The Enalos Suite generated 115 structurally similar compounds to salvianolic acid, rosmarinic acid, and quercetin. These compounds underwent IFD calculations, leading to the identification of two salvianolic acid analogues that exhibited strong binding to all the examined binding sites in both proteins, showcasing their potential as multi-target inhibitors. These findings introduce exciting possibilities for the development of novel therapeutic agents aiming to effectively disrupt the SARS-CoV-2 virus lifecycle.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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