Quinazoline-Schiff base conjugates: <i>in silico</i> study and ADMET predictions as multi-target inhibitors of coronavirus (SARS-CoV-2) proteins

Mansour, Mostafa A.; AboulMagd, Asmaa M.; Abdel‐Rahman, Hamdy M.

doi:10.1039/d0ra06424f

Cited by 48 publications

(49 citation statements)

References 53 publications

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“…To overcome this limitation we have operated the atomistic simulations which serve as a validation for the docking results. [47][48][49] Moreover, FPL is an efficient computational approach to assess ligand-binding affinity with a suitable time-consuming calculation. 50,51 Furthermore, the scheme was successfully applied to the monomeric SARS-CoV-2 Mpro system recently.…”

Section: Md-rened Investigationsmentioning

confidence: 99%

Binding of inhibitors to the monomeric and dimeric SARS-CoV-2 Mpro

et al. 2021

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Section: Md-rened Investigationsmentioning

confidence: 99%

Binding of inhibitors to the monomeric and dimeric SARS-CoV-2 Mpro

et al. 2021

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“…However, it should be noted that the dynamics of receptors were not considered in docking simulations, and the number of trial docking poses was small. To overcome this limitation we have operated the atomistic simulations which serve as a validation for the docking results [37][38][39] . Moreover, FPL is an efficient computational approach to assess ligand-binding affinity with a suitable time-consuming calculation.…”

Section: Md-refined Investigationsmentioning

confidence: 99%

Binding of Inhibitors to the Monomeric and Dimeric SARS-CoV-2 Mpro

Tam¹,

Nam²,

Quang³

et al. 2020

Preprint

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SARS-CoV-2 rapidly infects millions of people worldwide since December 2019. There is still no effective treatment for the virus, resulting in the death of more than one million of patients. Inhibiting the activity of SARS-CoV-2 main protease (Mpro), 3C-like protease (3CLP), is able to block the viral replication and proliferation. Although the dimer was shown to be the biologically active form of the SARS-CoV-2 Mpro, in this context, our study has revealed that <i>in silico</i> screening for inhibitors of SARS-CoV-2 Mpro can be reliably done using the monomeric structure of the receptor. Docking and fast pulling of ligand (FPL) simulations for both monomeric and dimeric forms correlate well with the corresponding experimental binding affinity data of 30 compounds. In particular, the correlation coefficients between computational and experimental binding free energy of the monomeric SARS-CoV-2 Mpro are approximately similar to the dimeric target. Moreover, the correlation coefficient between the rupture forces to binding free energy are roughly the same. Furthermore, the correlation coefficient between calculated metrics of the monomeric and dimeric SARS-CoV-2 Mpro is R = 0.74. Our study results show that it is possible to speed up computer-aided drug design for SARS-CoV-2 Mpro by focusing on the monomeric form instead of the larger dimeric one.

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“…Investigated compounds exhibited no correlation between the lipophilicity and drug permeability as measured by the previously reported (Caco-2) cell line assay. 46,47 According to the drug distribution prediction, compounds 11k and 12d have the best blood-brain barrier (BBB) permeability in comparison to other tested compounds. Results show that the investigated compounds were relatively active, inhibiting CYP2C19, CYP2C9, and CYP3A4.…”

Section: Molecular Docking Studymentioning

confidence: 99%