Insights into solvation effects, spectroscopic, Hirshfeld surface Analysis, reactivity analysis and anti-Covid-19 ability of doxylamine succinate: Experimental, DFT, MD and docking simulations

Al‐Otaibi, Jamelah S.; Mary, Y. Sheena; Mary, Y. Shyma; Acharjee, Nivedita; Balachandar, S.; Yathirajan, H. S.

doi:10.1016/j.molliq.2022.119609

Cited by 12 publications

(3 citation statements)

References 63 publications

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“…We then quantitated the RMSF to understand the flexibility per residue in the active sites of 3CL Pro and PL Pro in unbound and bound conformations with ligands (compounds 7 , 8 , and 9 ) [ 75 ]. In the absence of ligands, amino acid residues in the active sites of 3CL Pro and PL Pro showed higher flexibility, primarily due to the loop regions and terminal residues, which are dynamic and less controlled [ 11 , 76 , 77 ]. We found that the per-residue RMSF of ligand–target protein complexes was either reduced or showed nearby fluctuation levels, as observed in the unbound target, and it is in accordance with the fact that smaller-ligand RMSFs are deemed better [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CLPro and PLPro) by Molecular Docking and Dynamic Simulation Studies

Saquib,

Bakheit,

Ahmed

et al. 2024

Molecules

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We provide promising computational (in silico) data on phytochemicals (compounds 1–10) from Arabian Peninsula medicinal plants as strong binders, targeting 3-chymotrypsin-like protease (3CLPro) and papain-like proteases (PLPro) of SARS-CoV-2. Compounds 1–10 followed the Lipinski rules of five (RO5) and ADMET analysis, exhibiting drug-like characters. Non-covalent (reversible) docking of compounds 1–10 demonstrated their binding with the catalytic dyad (CYS145 and HIS41) of 3CLPro and catalytic triad (CYS111, HIS272, and ASP286) of PLPro. Moreover, the implementation of the covalent (irreversible) docking protocol revealed that only compounds 7, 8, and 9 possess covalent warheads, which allowed the formation of the covalent bond with the catalytic dyad (CYS145) in 3CLPro and the catalytic triad (CYS111) in PLPro. Root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and radius of gyration (Rg) analysis from molecular dynamic (MD) simulations revealed that complexation between ligands (compounds 7, 8, and 9) and 3CLPro and PLPro was stable, and there was less deviation of ligands. Overall, the in silico data on the inherent properties of the above phytochemicals unravel the fact that they can act as reversible inhibitors for 3CLPro and PLPro. Moreover, compounds 7, 8, and 9 also showed their novel properties to inhibit dual targets by irreversible inhibition, indicating their effectiveness for possibly developing future drugs against SARS-CoV-2. Nonetheless, to confirm the theoretical findings here, the effectiveness of the above compounds as inhibitors of 3CLPro and PLPro warrants future investigations using suitable in vitro and in vivo tests.

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Section: Discussionmentioning

confidence: 99%

Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CLPro and PLPro) by Molecular Docking and Dynamic Simulation Studies

Saquib,

Bakheit,

Ahmed

et al. 2024

Molecules

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“…In another report, Al-Otaibi et al studied the potential antiviral activity of doxylamine succinate against SARS-CoV-2 protease by its molecular docking studies and simulations. Moreover, it was claimed that the negative binding free energy might suggest the irreversibly bound cocrystal with the protein . In a similar study, Al-Otaibi et al reported molecular docking of three cocrystals of hydrochlorothiazide on glucocorticoid receptor, ionotropic glutamate receptor, peroxidase manganese dependent I, and staphylococcal peroxidase inhibitor proteins.…”

Section: An Outlook On the Applicability Of Molecular Docking Studies...mentioning

confidence: 99%

“…Moreover, it was claimed that the negative binding free energy might suggest the irreversibly bound cocrystal with the protein. 10 In a similar study, Al-Otaibi et al reported molecular docking of three cocrystals of hydrochlorothiazide on glucocorticoid receptor, ionotropic glutamate receptor, peroxidase manganese dependent I, and staphylococcal peroxidase inhibitor proteins. The study highlighted the potential inhibitory actions of the cocrystals on the ground binary complexes' binding energy.…”

Section: Molecular Docking Studies Involving Pharmaceutical Cocrystal...mentioning

confidence: 99%

Molecular Docking of Pharmaceutical Cocrystal As a Ligand: Do We Need to Rethink?

Roy

Pandey

Ghosh

2022

Crystal Growth & Design

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Molecular docking is a resourceful virtual screening tool for predicting the possible therapeutic activities of molecules and lowering the attrition rate at the early stage of drug design and development. Recently reports of molecular docking of cocrystals have been published to demonstrate their potential biological activities toward specific target proteins. Since regulatory bodies, e.g., U.S. FDA and EMA, do not identify cocrystal as a new molecular entity, it is not relevant to conduct such docking studies, especially in the case of orally administered cocrystals, by posing them as ligands instead of the parent API. This article showcases the noteworthy considerations regarding molecular docking studies of cocrystals as ligands.

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DFT, solvation effects, reactivity and SERS analysis on structural, optical, and vibrational properties of a biomolecule of pyrimidine derivative adsorbed on metal clusters of Ag/Au/Cu

Al‐Otaibi

Mary²,

Mary³

et al. 2022

Journal of the Indian Chemical Society

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Insights into solvation effects, spectroscopic, Hirshfeld surface Analysis, reactivity analysis and anti-Covid-19 ability of doxylamine succinate: Experimental, DFT, MD and docking simulations

Cited by 12 publications

References 63 publications

Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CLPro and PLPro) by Molecular Docking and Dynamic Simulation Studies

Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CLPro and PLPro) by Molecular Docking and Dynamic Simulation Studies

Molecular Docking of Pharmaceutical Cocrystal As a Ligand: Do We Need to Rethink?

DFT, solvation effects, reactivity and SERS analysis on structural, optical, and vibrational properties of a biomolecule of pyrimidine derivative adsorbed on metal clusters of Ag/Au/Cu

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