Pharmacophore development, drug-likeness analysis, molecular docking, and molecular dynamics simulations for identification of new CK2 inhibitors

Hammad, Sara; Bouaziz-Terrachet, Souhila; Meghnem, Rosa; Meziane, Dalila

doi:10.1007/s00894-020-04408-2

Cited by 22 publications

(12 citation statements)

References 62 publications

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“…Protein and protein-ligand complexes were solvated in a rectangular box of TIP3P waters. The obtained system was neutralized adding seven-sodium counter ions to neutralize the net negative charge of the protein, and then physiological conditions (298 K, pH 7.4, 0.9% NaCl solution) were established (Hammad et al, 2020).…”

Section: Simulationmentioning

confidence: 99%

Uncaria tomentosa(cat’s claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling

Yepes-Pérez

Herrera-Calderon

Quintero‐Saumeth

2020

Journal of Biomolecular Structure and Dynamics

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COVID-19 is a novel severe acute respiratory syndrome coronavirus. Currently, there is no effective treatment and vaccines seem to be the solution in the future. Virtual screening of potential drugs against the S protein of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has provided small molecular compounds with a high binding affinity. Unfortunately, most of these drugs do not attach with the binding interface of the receptor-binding domain (RBD)-angiotensin-converting enzyme-2 (ACE-2) complex in host cells. Molecular modeling was carried out to evaluate the potential antiviral properties of the components of the medicinal herb Uncaria tomentosa (cat's claw) focusing on the binding interface of the RBD-ACE-2 and the viral spike protein. The in silico approach starts with protein-ligand docking of 26 Cat's claw key components followed by molecular dynamics simulations and re-docked calculations. Finally, we carried out drug-likeness calculations for the most qualified cat's claw components. The structural bioinformatics approaches led to the identification of several bioactive compounds of U. tomentosa with potential therapeutic effect by dual strong interaction with interface of the RBD-ACE-2 and the ACE-2 binding site on SARS-CoV-2 RBD viral spike. In addition, in silico drug-likeness indices for these components were calculated and showed good predicted therapeutic profiles of these phytochemicals found in U. tomentosa (cat's claw). Our findings suggest the potential effectiveness of cat's claw as complementary and/or alternative medicine for COVID-19 treatment.

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Section: Simulationmentioning

confidence: 99%

Uncaria tomentosa(cat’s claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling

Yepes-Pérez

Herrera-Calderon

Quintero‐Saumeth

2020

Journal of Biomolecular Structure and Dynamics

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“…All complexes were initially solvated in a cubic box of TIP3P waters and then Na + and Cl − ions were added to neutralize the net atomic charge of the whole system by random replacement of water molecules. NaCl concentration was set to the physiological value of 0.15 M [21] . The size of the solvated spike trimer-ligand complexes was > 6, 66, 186 atoms.…”

Section: Materials and Methodologymentioning

confidence: 99%

Potential of phytocompounds from Brassica oleracea targeting S2-domain of SARS-CoV-2 spike glycoproteins: Structural and molecular insights

Jose

Gupta

Sharma

et al. 2022

Journal of Molecular Structure

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By 24th Sep. 2021, there are more than 229 million COVID-19 cases worldwide, the researchers are tirelessly working to discover and develop an efficient drug molecule against this devastative viral infection. This study aims to evaluate the inhibitory efficiency of the organic acids and phenolic compounds present in Brassica oleracea (Tronchuda Cabbage) against spike glycoprotein in SARS-CoV-2. Thirty-seven phytocompounds are screened on the basis of their molecular weight (<500 g/mol) and 14 ligands are docked using Autodock Vina and Autodock4 (version 4.2.6). The stability of the top five docked complexes was analyzed using classical molecular dynamics (MD) simulation. ADMET analysis is performed for the top five compounds and their targets are identified using SwissTargetPrediction. Phytoactives from B. oleracea namely Astragalin, 3-p-coumaroylquinic acid, 4-p-coumaroylquinic acid and sinapoyl-D-glucoside showed high binding affinities and free energy of binding during molecular docking and MD simulation studies (∼ 8.5-9.0 kcal/mol) for the spike glycoprotein trimer of SARS-CoV2. The ADMET analysis revealed that these phytocompounds have good solubility in the aqueous phase and that they don't penetrate the blood brain barrier. Moreover, there is no P-gp substrate inhibition, CYP1A2 inhibition, CYP2C19 inhibition, CYP2C9 inhibition, CYP2D6 inhibition and CYP3A4 inhibition observed for these compounds. Additionally, zero PAINS alerts were reported. These findings from molecular docking and MD simulation studies suggest that astragalin and coumaroylquinic acids from Tronchuda cabbage possess potential inhibitory capacity against spike glycoprotein trimer of SARS-CoV-2 and could be further taken up as lead targets for drug discovery.

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“…54 The PDB file of each compound was imported in iGEMDOCK software as ligand. As done in previous studies, 55 the active site was identified as a distance 8Ǻ from the center of bound ligand 1YN. All docking simulations were performed with accurate docking, population size of 800, 80 generations and number of solutions of 10. iGEMDOCK ranks and visualizes the screening compounds by combining the pharmacological interactions and energy-based scoring function.…”

Section: Molecular Docking Studymentioning

confidence: 99%

Design and One-Pot Synthesis of Some New [3,5-Di(4’,5’-diphenyl-2’-substituted)-1H-imidazol-1-yl)]-1H-1,2,4-triazole Derivatives: in silico ADMET and Docking Study, Antibacterial and Antifungal Activities Evaluation

Hadhoum¹,

Hadjadj-Aoul²,

Hocine³

et al. 2021

HETEROCYCLES

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In this paper, a new series of some [3,5-di(4',5'-diphenyl-2'substituted)-1H-imidazol-1-yl)]-1H-1,2,4-triazole derivatives (C1-C9) were efficiently synthesized by a one-pot three component reaction via a coupling of benzil, aldehydes and 3,5-diamino-1,2,4-triazole and using ceric ammonium nitrate as a catalyst. The structures of the newly compounds were investigated by IR, 1 H NMR, 13 C NMR and UV-visible spectroscopy. The in vitro antibacterial and antifungal activities showed that the C9 is the most active compound. The C9 docking study revealed the best mode of binding in the active site of the cytochrome P450 lanosterol 14α-demethylase. All the synthesized compounds were predicted as non-carcinogens and demonstrated acceptable pharmacokinetic profile in blood brain barrier (BBB) and human intestinal absorption (HIA).A series of some [3,5-di(4',5'-diphenyl-2'-substituted)-1H-imidazol-1-yl)]-1H-1,2,4-triazole derivatives (C1-C9, Table 1) were obtained by condensation of benzil, corresponding aldehydes and 3,5-diamino-1,2,4-triazole, the rationality of the design and the synthesis of the newly compounds are shown in Scheme 1. Scheme 1. Design and synthesis of [3,5-di (4',5'-diphenyl-2'-substituted)-1H-imidazol-1-yl)]-1H-1,2,4triazole derivatives

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Pharmacophore development, drug-likeness analysis, molecular docking, and molecular dynamics simulations for identification of new CK2 inhibitors

Cited by 22 publications

References 62 publications

Uncaria tomentosa(cat’s claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling

Uncaria tomentosa(cat’s claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling

Potential of phytocompounds from Brassica oleracea targeting S2-domain of SARS-CoV-2 spike glycoproteins: Structural and molecular insights

Design and One-Pot Synthesis of Some New [3,5-Di(4’,5’-diphenyl-2’-substituted)-1H-imidazol-1-yl)]-1H-1,2,4-triazole Derivatives: in silico ADMET and Docking Study, Antibacterial and Antifungal Activities Evaluation

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