Identification of natural inhibitors against Mpro of SARS-CoV-2 by molecular docking, molecular dynamics simulation, and MM/PBSA methods

Sharma, Priyanka; Joshi, Tushar; Mathpal, Shalini; Joshi, Tanuja; Pundir, Hemlata; Chandra, Subhash; Tamta, Sushma

doi:10.1080/07391102.2020.1842806

Cited by 28 publications

(19 citation statements)

References 26 publications

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“…The interactions are highly favoured by Van der Waal interactions and electrostatic interactions together. Polar solvation energy individually dominates the binding energy [ 56 , 57 ].…”

Section: Resultsmentioning

confidence: 99%

In silico screening of antiviral compounds from Moringa oleifera for inhibition of SARS-CoV-2 main protease

Sivani

Venkatesh

Murthy

et al. 2021

Current Research in Green and Sustainable Chemistry

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COVID-19 as per early April 2021, has globally exceeded 129 million cases and is the cause of about 2.8 million deaths. Since the illness is known to have a wide array of symptoms, in addition to its ability to spread rapidly through contact and the complexity involved in developing drugs, there is an immediate need to look into alternative treatment regimes. This study was intended to identify potential antiviral compounds from Moringa oleifera against the selected target main protease (M pro ), which is vital for the survival of the virus. In silico molecular docking and dynamics was performed to determine a potential inhibitor against M pro . Phytochemicals of Moringa olifera reported in literature were retrieved from public databases and employed for molecular docking studies against M pro . PyRx software was used to perform docking analysis. Visualization of amino acid interactions between the ligand and target was performed using Maestro and Discovery studio visualizer to analyze the type of interactions. Compounds displaying high binding affinities were subjected for analysis of pharmacokinetic studies, later molecular dynamics (MD) and MM-PBSA studies was conducted over selected compounds using GROMACS. Rutin and Isorhamnetin-3-O-rutinoside, both flavonoids thoroughly studied for their medicinal properties showcased strong interactions and the highest binding affinity of −8.9 kcal/mol with the M pro . The binding energy calculated employing MM-PBSA for Rutin and Isorhamnetin-3-O-rutinoside were −86.832 kJ/mol and −72.984 kJ/mol, respectively. The overall studies revealed that Rutin and Isorhamnetin-3-O-rutinoside are portenial in inhibiting the SARS-CoV-2 M pro and can be validated through in-vitro and in-vivo studies.

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“…The interactions are highly favoured by Van der Waal interactions and electrostatic interactions together. Polar solvation energy individually dominates the binding energy [ 56 , 57 ].…”

Section: Resultsmentioning

confidence: 99%

In silico screening of antiviral compounds from Moringa oleifera for inhibition of SARS-CoV-2 main protease

Sivani

Venkatesh

Murthy

et al. 2021

Current Research in Green and Sustainable Chemistry

View full text Add to dashboard Cite

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“…There are many reports on the use of molecular docking/in-silico studies to investigate the effectiveness of different types of drugs/molecules to inhibit the replication of the SARS-COV-2 main protease (Mpro). The effective binding of different phytochemicals, biomolecules, drugs and drug-like molecules have been examined and found that majority of the molecules investigated above does not bind to all the active sites effectively (Abu-Saleh et al 2020 ; Amin et al 2020 ; Basu et al 2020 ; Cavasotto and Filippo 2020 ; Choudhary et al 2020a , b ; Lokhande et al 2020 ; Peele et al 2020 ; Sharma et al 2020 ; Tallei et al 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…(Abu-Saleh et al 2020;Amin et al 2020;Basu et al 2020; Cavasotto and Filippo 2020; Choudhary et al 2020a, b;Lokhande et al 2020;Peele et al 2020;Sharma et al 2020;Tallei et al 2020). …”

mentioning

confidence: 99%

Binding ability of arginine, citrulline, N-acetyl citrulline and thiocitrulline with SARS COV-2 main protease using molecular docking studies

Narayan

2021

Netw Model Anal Health Inform Bioinforma

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In this article, the binding abilities of arginine, citrulline, N -acetyl citrulline and thiocitrulline on the active sites of SARS-COV-2 protease have been investigated using in-silico studies. All the above ligands bind selectively and preferentially to Cys-145 active site and also to other amino acids surrounding to it in the main protease. Of which arginine forms less number of weaker bonds compared to the other ligands, it by itself is a precursor for the formation of citrulline analogues with in the cell. Major advantage of using the above ligands is that in addition to its preferential binding, they have the ability to increase the immunity by assisting NO generation. Our results show that N -acetyl citrulline, citrulline, thiocitrulline and arginine may be used as a supplement during the treatment of SARS-COV-2.

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“…The oxo group at the 14th position and the carbonyl oxygen of carboxylic acid at the second position of icosahydropicene-2-carboxylic acid core nucleus of GA exhibited conventional hydrogen bond interactions with the amino group of GLN189 (3.01 and 2.19 Å, respectively). Further, hydrophobic alkyl interactions were observed between the icosahydropicene-2-carboxylic acid core nucleus methyl groups of GA with CYS145 ( Several literature evidences are implicating that SARS-CoV-2 M pro could be used for screening purposes to predict the binding affinity of the approved drugs, natural inhibitors, and those in clinical trials [5,[42][43][44]. The binding stability of an α-ketoamide inhibitor O6K or 13b as reference control inside the SARS-CoV-2 M pro was carried out to assess affinity score and determine theoretically the possible and probable active site residues involved in the formation of complex, which was found consistent with our observation [44][45][46][47].…”

Section: Binding Interactions Of Potential Antiviral Agents At the Acmentioning

confidence: 99%

Molecular docking, binding mode analysis, molecular dynamics, and prediction of ADMET/toxicity properties of selective potential antiviral agents against SARS-CoV-2 main protease: an effort toward drug repurposing to combat COVID-19

et al. 2021

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The importance of the main protease (M pro) enzyme of SARS-CoV-2 in the digestion of viral polyproteins introduces M pro as an attractive drug target for antiviral drug design. This study aims to carry out the molecular docking, molecular dynamics studies, and prediction of ADMET properties of selected potential antiviral molecules. The study provides an insight into biomolecular interactions to understand the inhibitory mechanism and the spatial orientation of the tested ligands and further, identification of key amino acid residues within the substrate-binding pocket that can be applied for structure-based drug design. In this regard, we carried out molecular docking studies of chloroquine (CQ), hydroxychloroquine (HCQ), remdesivir (RDV), GS441524, arbidol (ARB), and natural product glycyrrhizin (GA) using AutoDock 4.2 tool. To study the drug-receptor complex's stability, selected docking possesses were further subjected to molecular dynamics studies with Schrodinger software. The prediction of ADMET/toxicity properties was carried out on ADMET Prediction™. The docking studies suggested a potential role played by CYS145, HIS163, and GLU166 in the interaction of molecules within the active site of COVID-19 M pro. In the docking studies, RDV and GA exhibited superiority in binding with the crystal structure of M pro over the other selected molecules in this study. Spatial orientations of the molecules at the active site of M pro exposed the significance of S1-S4 subsites and surrounding amino acid residues. Among GA and RDV, RDV showed better and stable interactions with the protein, which is the reason for the lesser RMSD values for RDV. Overall, the present in silico study indicated the direction to combat COVID-19 using FDA-approved drugs as promising agents, which do not need much toxicity studies and could also serve as starting points for lead optimization in drug discovery.

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Identification of natural inhibitors against Mpro of SARS-CoV-2 by molecular docking, molecular dynamics simulation, and MM/PBSA methods

Cited by 28 publications

References 26 publications

In silico screening of antiviral compounds from Moringa oleifera for inhibition of SARS-CoV-2 main protease

In silico screening of antiviral compounds from Moringa oleifera for inhibition of SARS-CoV-2 main protease

Binding ability of arginine, citrulline, N-acetyl citrulline and thiocitrulline with SARS COV-2 main protease using molecular docking studies

Molecular docking, binding mode analysis, molecular dynamics, and prediction of ADMET/toxicity properties of selective potential antiviral agents against SARS-CoV-2 main protease: an effort toward drug repurposing to combat COVID-19

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