Computational repurposing of tamibarotene against triple mutant variant of SARS-CoV-2

Mujwar, Somdutt

doi:10.1016/j.compbiomed.2021.104748

Cited by 56 publications

(45 citation statements)

References 29 publications

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“…The binding interactions of the ligand within the macromolecular site were separated into four groups throughout the simulation procedure: hydrogen bonds, hydrophobic interactions, ionic interactions, and water interaction bridges. The radius of gyration (rGyR), molecular surface area (MolSA), solvent accessible surface area (SASA), and polar surface area of the ligands were all measured (PSA) [ 63 – 65 ]. In comparison to its initial frame, the RMSD value of the ligand molecule was determined throughout the whole simulation duration.…”

Section: Methodsmentioning

confidence: 99%

In silico bioprospecting of taraxerol as a main protease inhibitor of SARS-CoV-2 to develop therapy against COVID-19

Mujwar

Harwansh

2022

Struct Chem

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COVID-19 was caused by a novel coronavirus known as SARS-CoV-2. The COVID-19 disease outbreak has been avowed as a global pandemic by the World Health Organization at the end of March 2020. It leads to the global economic crash, resulting in the starvation of a large population belonging to economically backward countries. Hence, the development of an alternative medicine along with the vaccine is of the utmost importance for the management of COVID-19. Therefore, screening of several herbal leads was performed to explore their potential against SARS-CoV-2. Furthermore, viral main protease was selected as a key enzyme for performing the study. Various computational approaches, including molecular docking simulation, were used in the current study to find potential inhibitors of viral main protease from a library of 150 herbal leads. Toxicity and ADME prediction of selected molecules were also analysed by Osiris molecular property explorer software. Molecular dynamic simulation of the top 10 docked herbal leads was analysed for stability using 100 ns. Taraxerol (−10.17 kcal/mol), diosgenin (10.12 kcal/mol), amyrin (−9.56 kcal/mol), and asiaticoside (−9.54 kcal/mol) were among the top four herbal leads with the highest binding affinity with the main protease enzyme. Thus, taraxerol was found to be an effective drug candidate against the main protease enzyme for the management of COVID-19. Furthermore, its clinical effect and safety profile need to be established through an in vivo model. Supplementary information The online version contains supplementary material available at 10.1007/s11224-022-01943-x.

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Section: Methodsmentioning

confidence: 99%

In silico bioprospecting of taraxerol as a main protease inhibitor of SARS-CoV-2 to develop therapy against COVID-19

Mujwar

Harwansh

2022

Struct Chem

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“…Surprisingly, the affinity of the Glycyrrhizin slightly decreased against the spike protein variants, though it still shows considerable binding energy and dissociation constant ( Figure S6 ). Catechins and tamibarotene have been found to interact strongly with the UK variant and triple SARS-CoV-2 variant [ 98 , 99 ].…”

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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“…The radius of gyration (rGyR), molecular surface area (MolSA), solvent accessible surface area (SASA), and polar surface area of the ligands were all measured (PSA). [55][56][57] In comparison to its initial frame, the RMSD value of the ligand molecule was determined throughout the whole simulation duration. PSA was determined by taking into consideration the total contribution of oxygen and nitrogen atoms, whereas the ligand's extended length, which correlates to its main moment of inertia, was computed using a 1.4 probe radius.…”

Section: Molecular Dynamic Simulationmentioning

confidence: 99%

“…The exact grid coordinates were obtained from our previously published study on the same protein. [58,55,42,44,40] The docking results for the complex inhibitor N3 against viral macromolecular target were tabulated in Table 1. The lead molecules were chosen based on their a nity for the viral main protease enzyme.…”

Section: Molecular Docking Simulationmentioning

confidence: 99%

In-silico bioprospecting of taraxerol as a main protease inhibitor of SARS-CoV-2 to develop therapy against COVID-19

Mujwar

Harwansh

2022

Preprint

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The coronavirus disease outbreak towards the end of 2019 was caused by a novel coronavirus known as SARS-CoV-2. The COVID-19 disease outbreak has been avowed as a global pandemic by the World Health Organization by the end of March 2020. The COVID-19 pandemic was responsible for the crash of the global economy, resulting in the starvation of a large population belonging to economically backward countries. Thus, the global pandemic situation demands the development of a novel antiviral therapy against COVID-19. In the current study, screening of the ligands from the herbal source was performed to explore potential leads through targeting the viral main protease enzyme of SARS-CoV-2. Taraxerol was found to be a potential antagonist of the viral main protease enzyme. Thus, the present article was aimed at investigating taraxerol as a potent herbal lead by toxicity and ADME prediction for the management of COVID-19.

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Computational repurposing of tamibarotene against triple mutant variant of SARS-CoV-2

Cited by 56 publications

References 29 publications

In silico bioprospecting of taraxerol as a main protease inhibitor of SARS-CoV-2 to develop therapy against COVID-19

In silico bioprospecting of taraxerol as a main protease inhibitor of SARS-CoV-2 to develop therapy against COVID-19

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

In-silico bioprospecting of taraxerol as a main protease inhibitor of SARS-CoV-2 to develop therapy against COVID-19

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