In-silico screening and identification of potential inhibitors against 2Cys peroxiredoxin of<i>Candidatus</i>Liberibacter asiaticus

Gupta, Deena Nath; Dalal, Vikram; Savita, Brajesh Kumar; Dhankhar, Poonam; Ghosh, Dilip K.; Kumar, Pravindra; Sharma, Ashwani

doi:10.1080/07391102.2021.1916597

Cited by 13 publications

(15 citation statements)

References 72 publications

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“…Homology modeling was carried out using previously reported protocols [ 40 , 41 ]. Briefly, structures of SARS-CoV-2 nsp16 in complex with the inhibitors SS148 and WZ16 and structures of SARS-CoV, MERS-CoV, and HCoV-OC43 nsp16 in complex with sinefungin were retrieved from the Protein Data Bank ( https://www.rcsb.org ) using the entries 7R1T, 7R1U [ 28 ], 2XYR [ 19 ], 5YNB, and 7NH7 [ 29 ], respectively.…”

Section: Methodsmentioning

confidence: 99%

SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses

Li¹,

Ghiabi²,

Klíma³

et al. 2023

Biochimica et Biophysica Acta (BBA) - General Subjects

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Section: Methodsmentioning

confidence: 99%

SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses

Li¹,

Ghiabi²,

Klíma³

et al. 2023

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…The molecular mechanics Poisson–Boltzmann surface area (MMPBSA) method was utilized to determine the binding affinity of FmtA–drug(s) complexes. − Here, a total of 2000 snapshots from the last 20 ns of molecular dynamics were utilized to calculate the binding energy of FmtA–gemifloxacin, FmtA–paromomycin, FmtA–streptomycin, and FmtA–tobramycin complexes . The per residue decomposition analysis was performed to calculate the binding energy contribution of active site residues with the ligand in FmtA–drug(s) complexes. , …”

Section: Methodsmentioning

confidence: 99%

“…DFT calculation was done to evaluate the polarity of drugs (gemifloxacin, paromomycin, streptomycin, and tobramycin) . The molecular electrostatic potential and molecular orbital energies were assessed by using B3LYP with the basis set of 6-311G (d,p), as done by Dalal et al ,,,, Furthermore, quantum mechanics/molecular mechanics (QM/MM) estimations for FmtA–drug(s) complexes were conducted using our own N-layered integrated molecular orbital and molecular mechanics (ONIOM) method, as done by Dalal et al ,,, The inhibitor and side chain atoms of Ser127, Lys130, Tyr211, and Asp213 were considered in the QM layer, whereas the remaining part of the protein was put in the MM layer. The enthalpy (Δ H ), relative Gibbs free energy (Δ G ), and entropy (Δ S ) were assessed by ONIOM (B3LYP/6-311G(d,p): AMBER).…”

Section: Methodsmentioning

confidence: 99%

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Drug-Repurposing Approach To Combat Staphylococcus aureus: Biomolecular and Binding Interaction Study

et al. 2022

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Staphylococcus aureus is considered as one of the most widespread bacterial pathogens and continues to be a prevalent cause of mortality and morbidity across the globe. FmtA is a key factor linked with methicillin resistance in S. aureus. Consequently, new antibacterial compounds are crucial to combat S. aureus resistance. Here, we present the virtual screening of a set of compounds against the available crystal structure of FmtA. The findings indicate that gemifloxacin, paromomycin, streptomycin, and tobramycin were the top-ranked potential drug molecules based on the binding affinity. Furthermore, these drug molecules were analyzed with molecular dynamics simulations, which showed that the identified molecules formed highly stable FmtA–inhibitor(s) complexes. Molecular mechanics Poisson–Boltzmann surface area and quantum mechanics/molecular mechanics calculations suggested that the active site residues (Ser127, Lys130, Tyr211, and Asp213) of FmtA are crucial for the interaction with the inhibitor(s) to form stable protein–inhibitor(s) complexes. Moreover, fluorescence- and isothermal calorimetry-based binding studies showed that all the molecules possess dissociation constant values in the micromolar scale, revealing a strong binding affinity with FmtAΔ80, leading to stable protein–drug(s) complexes. The findings of this study present potential beginning points for the rational development of advanced, safe, and efficacious antibacterial agents targeting FmtA.

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“…RMSD, radius of gyration (Rg), root-mean-square fluctuations (RMSFs), surface accessibility surface area (SASA), intermolecular hydrogen bonding, hydrogen bonding between protein and ligand, and contact maps were generated using the resultant MD trajectories of CCL2− Catechin complexes. 30 2.8. Statistical Analysis.…”

Section: Molecular Dynamics (Md) Simulationmentioning

confidence: 99%

Gallate Moiety of Catechin Is Essential for Inhibiting CCL2 Chemokine-Mediated Monocyte Recruitment

Tripathi

Nagar

Kumar

et al. 2023

J. Agric. Food Chem.

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Leukocyte recruitment witnesses an orchestrated complex formation between the chemokines and their molecular partners. CCL2 chemokine that regulates monocyte trafficking is a worthwhile system from the pharmaceutical perspective. In the current study, four major catechins (EC/EGC/ECG/EGCG) were assessed for their inhibitory potential against CCL2-regulated monocyte/macrophage recruitment. Interestingly, catechins with the gallate moiety (ECG/EGCG) could only attenuate the CCL2induced macrophage migration. These molecules specifically bound to CCL2 on a pocket comprising the N-terminal, β 0 -sheets, and β 3 -sheets, and the binding affinity of ECGC (K d = 22 ± 4 μM) is ∼4 times higher than that of the ECG complex (K d = 85 ± 6 μM). MD simulation analysis evidenced that the molecular specificity/stability of CCL2−catechin complexes is regulated by multiple factors, including stereospecificity, number of hydroxyl groups on the annular ring-B, the positioning of the carbonyl group, and the methylation of the galloyl ring. Further, a significant overlap on the binding surface of CCL2 for EGCG/ECG and receptor interactions as evidenced from NMR data provided the rationale for the observed inhibition of macrophage migration in response to EGCG/ECG binding. In summary, these galloylated epicatechins can be considered as potent protein−protein interaction (PPI) inhibitors that regulate CCL2-directed leukocyte recruitment for resolving inflammatory/immunomodulatory disorders.

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In-silico screening and identification of potential inhibitors against 2Cys peroxiredoxin ofCandidatusLiberibacter asiaticus

Cited by 13 publications

References 72 publications

SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses

SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses

Drug-Repurposing Approach To Combat Staphylococcus aureus: Biomolecular and Binding Interaction Study

Gallate Moiety of Catechin Is Essential for Inhibiting CCL2 Chemokine-Mediated Monocyte Recruitment

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