Virtual screening, ADMET prediction and dynamics simulation of potential compounds targeting the main protease of SARS-CoV-2

Yadav, Rohitash; Imran, Mohammed; Dhamija, Puneet; Chaurasia, Dheeraj Kumar; Handu, Shailendra

doi:10.1080/07391102.2020.1796812

Cited by 43 publications

(18 citation statements)

References 68 publications

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“…They can form metal complexes with Fe(II), Ni(II), Zn(II) and Cu(II) ions as an inhibitor for COVID-19. [24][25][26] Recently, our lab has synthesized several novel metal complexes possing good optoelectronic properties. [10][11][12] Unlike the previous several studies, we have synthesized a novel copper (II) complex [Cu(phen) 3 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Copper(II) Coordination Complex, Its Molecular Docking and Computational Exploration for Novel Functional Properties: A Dual Approach

et al. 2021

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The present investigation uses a dual approach to study the copper (II) complex [Cu(phen) 3 ]. (ClO 4) 2 .HL.CH 3 CN (1) and its cationic complex-[Cu(II)(phen) 3 ] 2 + (1 a), where, HL = 4-Bromo-2((Z)-(naphthalene-4-ylimino)methyl)phenol, phen = 1,10-phenanthroline. The complex (1) crystallized in the triclinic system of the space group P-1 with two molecules in the unit cell and reveals a distorted octahedral geometry. Inspiring by recent developments to find a potential inhibitor for the COVID-19 virus, we have also performed molecular docking study of [Cu(phen) 3 ] + 2 to see if our novel complex shows an affinity for the main protease (M pro) of COVID-19 spike protein. Interestingly, the results are found quite encouraging where the binding affinity and inhibition constant were found to be À 8.400 kcal/mol and 0.661 μM, respectively, for the bestdocked confirmation of [Cu(II)(Phen) 3 ] + 2 complex with M pro protein. This binding affinity is reasonably well as compared to recently known antiviral drugs. For instance, the binding affinity of [Cu(II)(Phen) 3 ] + 2 complex is found to be better than recently docking results of chloroquine (À 6.293 kcal/mol), hydroxychloroquine (À 5.573 kcal/mol) and remdesivir (À 6.352 kcal/mol) with M pro protein. Thus, we believe the broad-spectrum functional properties of our complex will provoke not only the interest of material chemists in materials designing but also incite the drug designing community.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Copper(II) Coordination Complex, Its Molecular Docking and Computational Exploration for Novel Functional Properties: A Dual Approach

et al. 2021

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“…This study enabled them to identify potential drugs that would block the ACE2 and Spike protein interactions by binding at the ACE2–Spike interface (Smith and Smith 2020 ). Computational studies on receptor binding site prediction and ligand screening based on the ADMET properties have been performed earlier (Yadav et al 2020 ). The role of plant derivatives/phytochemicals from medicinally important plants and potential small molecules, against multiple SARS-CoV-2 drug targets have also been explored using the molecular docking and dynamics approaches (Das et al 2020 ; Pandey et al 2020 ; Sharma and Shanavas 2020 ; Fatoki et al 2020 ; Jiménez-Alberto et al 2020 ; Liang et al 2020 ; Meyer-Almes 2020 ).…”

Section: Introductionmentioning

confidence: 99%

An insight into the inhibitory mechanism of phytochemicals and FDA-approved drugs on the ACE2–Spike complex of SARS-CoV-2 using computational methods

et al. 2021

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The S-glycoprotein (Spike) of the SARS-CoV-2 forms a complex with the human transmembrane protein angiotensin-converting enzyme 2 (ACE2) during infection. It forms the first line of contact with the human cell. The FDA-approved drugs and phytochemicals from Indian medicinal plants were explored. Molecular docking and simulations of these molecules targeting the ACE2–Spike complex were performed. Rutin DAB10 and Swertiapuniside were obtained as the top-scored drugs as per the docking protocol. The MD simulations of ligand-free, Rutin DAB10-bound, and Swertiapuniside-bound ACE2–Spike complex revealed abrogation of the hydrogen bonding network between the two proteins. The principal component and dynamic cross-correlation analysis pointed out conformational changes in both the proteins unique to the ligand-bound systems. The interface residues, His34, and Lys353 from ACE2 and Arg403, and Tyr495 from the Spike protein formed significant strong interactions with the ligand molecules, inferring the inhibition of ACE2–Spike complex. Few novel interactions specific to Rutin-DAB10 and Swertiapuniside were also identified. The conformational flexibility of the drug-binding pocket was captured using the RMSD-based clustering of the ligand-free simulations. Ensemble docking was performed wherein the FDA-approved database and phytochemical dataset were docked on each of the cluster representatives of the ACE2–Spike. The phytochemicals identified belonged to Withania somnifera , Swertia chirayita , Tinospora cordifolia and Rutin DAB10, fulvestrant, elbasvir from FDA. Supplementary Information The online version contains supplementary material available at 10.1007/s11696-021-01680-1.

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“…Remdesivir and ritonavir/lopinavir, ribonucleotide analogs, have also been found to be capable of interfering with the working of RdRp, and therefore constitute another set of effective candidate drugs against the current pandemic (Figure 3) [54][55][56]. Furthermore, several in silico analyses are also being carried out to find novel drugs and/or bioactive natural compounds to treat COVID-19 [57][58][59][60][61][62]. Apart from therapeutic antibodies, SARS-CoV-2-specific proteins and processes, favoring the infectious virus, may also be targeted using well established small molecules, such as aloxistatin, chloroquine/hydroxychloroquine, anti-viral nucleotide analogs (remdesivir), protease inhibitors (lopinavir and ritonavir), antiviral phytochemicals, and the broad-spectrum antiviral drugs like favipiravir and arbidol.…”

Section: Potential Therapeutic Targets On Sars-cov-2mentioning

confidence: 99%

Host Cell and SARS-CoV-2-Associated Molecular Structures and Factors as Potential Therapeutic Targets

Chaudhary

Yadav

Chaudhary

et al. 2021

Cells

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Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute respiratory syndrome-related coronavirus. This viral disease is characterized by a myriad of varying symptoms, such as pyrexia, cough, hemoptysis, dyspnoea, diarrhea, muscle soreness, dysosmia, lymphopenia and dysgeusia amongst others. The virus mainly infects humans, various other mammals, avian species and some other companion livestock. SARS-CoV-2 cellular entry is primarily accomplished by molecular interaction between the virus’s spike (S) protein and the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), although other host cell-associated receptors/factors, such as neuropilin 1 (NRP-1) and neuropilin 2 (NRP-2), C-type lectin receptors (CLRs), as well as proteases such as TMPRSS2 (transmembrane serine protease 2) and furin, might also play a crucial role in infection, tropism and pathogenesis and clinical outcome. Furthermore, several structural and non-structural proteins of the virus themselves are very critical in determining the clinical outcome following infection. Considering such critical role(s) of the abovementioned host cell receptors, associated proteases/factors and virus structural/non-structural proteins (NSPs), it may be quite prudent to therapeutically target them through a multipronged clinical regimen to combat the disease.

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Virtual screening, ADMET prediction and dynamics simulation of potential compounds targeting the main protease of SARS-CoV-2

Cited by 43 publications

References 68 publications

Synthesis of Copper(II) Coordination Complex, Its Molecular Docking and Computational Exploration for Novel Functional Properties: A Dual Approach

Synthesis of Copper(II) Coordination Complex, Its Molecular Docking and Computational Exploration for Novel Functional Properties: A Dual Approach

An insight into the inhibitory mechanism of phytochemicals and FDA-approved drugs on the ACE2–Spike complex of SARS-CoV-2 using computational methods

Host Cell and SARS-CoV-2-Associated Molecular Structures and Factors as Potential Therapeutic Targets

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