In Silico Identification of Potential Allosteric Inhibitors of the SARS-CoV-2 Helicase

Rowaiye, Adekunle Babajide; Onuh, Olukemi; Asala, Titilayo; Ogu, Amoge; Bur, Daniel; Nwankwo, Ezinne; Orji, Uchenna; Ibrahim, Zainab; Hamza, Jamila; Ugorji, Adaku

doi:10.26434/chemrxiv.12570551.v1

Cited by 2 publications

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“…In this study, Glycyrrhizin binds to an allosteric site near the catalytic cleft, while Glycyrrhetinic acid interacts with residues in stalk and 1B domain. Triphenyamine and Darunavir have been reported to bind the same active site [ 102 ]. Rutin, xanthones, and many other polyphenols have been reported to be ATPase inhibitors [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Natural Antioxidants against SARS-CoV-2? Insights from the In-Silico World

et al. 2021

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The SARS CoV-2 pandemic has affected millions of people around the globe. Despite many efforts to find some effective medicines against SARS CoV-2, no established therapeutics are available yet. The use of phytochemicals as antiviral agents provides hope against the proliferation of SARS-CoV-2. Several natural compounds were analyzed by virtual screening against six SARS CoV-2 protein targets using molecular docking simulations in the present study. More than a hundred plant-derived secondary metabolites have been docked, including alkaloids, flavonoids, coumarins, and steroids. SARS CoV-2 protein targets include Main protease (MPro), Papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), Spike glycoprotein (S), Helicase (Nsp13), and E-Channel protein. Phytochemicals were evaluated by molecular docking, and MD simulations were performed using the YASARA structure using a modified genetic algorithm and AMBER03 force field. Binding energies and dissociation constants allowed the identification of potentially active compounds. Ligand-protein interactions provide an insight into the mechanism and potential of identified compounds. Glycyrrhizin and its metabolite 18-β-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp. The use of identified phytochemicals may help to speed up the drug development and provide natural protection against SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Natural Antioxidants against SARS-CoV-2? Insights from the In-Silico World

et al. 2021

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“…The PCA is used to statistically evaluate the various structural conformations of a protein generated during trajectories [69]. This study found that the BrucMetRS -Isopteropodin complex has the greatest global (total and average) motions of any holo structures, closely followed by the BrMelMetRS-OOU complex.…”

Section: Analyses Of Time-resolved Trajectoriesmentioning

confidence: 99%

Identifying potential natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silico approach

Rowaiye

Ogugua

Ibeanu³

et al. 2021

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Background: Brucellosis is an infectious disease caused by bacteria of the genus Brucella. Although it is the most common zoonosis worldwide, there are increasing reports of drug resistance and cases of relapse after long term treatment with the existing drugs of choice. This study therefore aims at identifying possible natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silico approach. Methods: Using PyRx 0.8 virtual screening software, the target was docked against a library of natural compounds obtained from edible African plants. The compound, 2-({3-[(3,5-dichlorobenzyl) amino] propyl} amino) quinolin-4(1H)-one (OOU) which is a co-crystallized ligand with the target was used as the reference compound. Screening of the molecular descriptors of the compounds for bioavailability, pharmacokinetic properties, and bioactivity was performed using the SWISSADME, pkCSM, and Molinspiration web servers respectively. The Fpocket and PLIP webservers were used to perform the analyses of the binding pockets and the protein ligand interactions. Analysis of the time-resolved trajectories of the Apo and Holo forms of the target was performed using the Galaxy and MDWeb servers. The lead compounds, Strophanthidin and Isopteropodin are present in Corchorus olitorius and Uncaria tomentosa (cat-claw) plants respectively. Results: Isopteropodin had a binding affinity score of -8.9 kcal / ml with the target and had 17 anti-correlating residues in pocket 1 after molecular dynamics simulation. The complex formed by Isopteropodin and the target had a total RMSD of 4.408 and a total RMSF of 9.8067. However, Strophanthidin formed 3 hydrogen bonds with the target at ILE21, GLY262 and LEU294, and induced a total RMSF of 5.4541 at Pocket 1. Conclusion: Overall, Isopteropodin and Strophanthidin were found to be better drug candidates than OOU and they showed potentials to inhibit the Brucella melitensis Methionyl-tRNA synthetase at Pocket 1, hence abilities to treat brucellosis. In vivo and in vitro investigations are needed to further evaluate the efficacy and toxicity of the lead compounds.

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In Silico Identification of Potential Allosteric Inhibitors of the SARS-CoV-2 Helicase

Cited by 2 publications

References 49 publications

Effectiveness of Natural Antioxidants against SARS-CoV-2? Insights from the In-Silico World

Effectiveness of Natural Antioxidants against SARS-CoV-2? Insights from the In-Silico World

Identifying potential natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silico approach

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