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Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein

Moschovou et al., International Journal of Molecular Sciences, doi:10.3390/ijms242115894
Nov 2023  
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In Silico molecular docking and molecular dynamics analysis identifying curcumin, quercetin, rosmarinic acid, and salvianolic acid B as having favorable binding to Mpro and three distinct sites on the S protein. Molecular dynamics simulations confirmed rosmarinic acid and quercetin's stable binding to Mpro. At the S protein sites, salvianolic acid B and rosmarinic acid formed robust complexes. A similarity search yielded compounds structurally related to the top binders, with two analogs of salvianolic acid emerging as promising multi-target inhibitors against both Mpro and S proteins.
This study includes quercetin and curcumin.
Moschovou et al., 2 Nov 2023, peer-reviewed, 7 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein
Kalliopi Moschovou, Maria Antoniou, Eleni Chontzopoulou, Konstantinos D Papavasileiou, Georgia Melagraki, Antreas Afantitis, Thomas Mavromoustakos
International Journal of Molecular Sciences, doi:10.3390/ijms242115894
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 "proteinligand" 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.
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