1. Insighting the Therapeutic Potential of Fifty (50) Shogaol Derivatives Against Mpro of SARS-CoV-2.
- Author
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Muhammad, Shabbir, Amin, Saniyah, Iqbal, Javed, Al-Sehemi, Abdullah G., Alarfaji, Saleh S., Ilyas, Mubashar, Atif, Muhammad, and Ullah, Sami
- Subjects
SARS-CoV-2 ,MOLECULAR docking ,INTERMOLECULAR interactions ,ANALYTICAL chemistry ,BINDING energy ,COVID-19 ,LIGAND binding (Biochemistry) ,ANTIVIRAL agents - Abstract
SARS-CoV-2, which causes COVID-19 disease, has proven to be a disastrous pandemic due to its contagious nature. This study has been planned to theoretically explore some antidotes against this virus from natural compounds. A total of 150 compounds from the shogaol class and shogaol derivatives (SDs) have been screened whereas 50 among those, which obeyed Lipinski's Rule of Five (Ro5), have further been investigated using molecular docking techniques. Furthermore, reference antiviral drug chloroquine (ChQ) and Co-Crystallized inhibitor have also been studied against M
pro of SARS-CoV-2 for comparing the potential of our docked ligands. Surprisingly, 78% of our docked ligands have shown binding energies and inhibition constants lower than ChQ and all ligands showed these values lower than an inhibitor. We further visualized the nature of intermolecular interactions for the best docked six ligands, which have shown higher binding affinities. We have also assessed ADMET properties for three ligands that displayed visually the best intermolecular interactions. Quantum analysis of three selected ligands L4, L5, and L9 has proved their reactivity and kinetic stability. Moreover, molecular dynamic simulations over 60 ns have been run for free Mpro and its selected three ligand-protein complexes for evaluating conformational stability and residual flexibility of docked complexes. Furthermore, 100 ns the MD simulations have been performed for two ligand complexes L4, L5 (with negative binding free energy), and inhibitor. Available parameters suggest stable complexes for our ligands and could be active drugs against SARS-CoV-2 in near future. A total of 50 shogaol derivatives (SDs) which obeyed Lipinski's rule of five (Ro5) have been investigated using molecular docking and dynamic techniques. We have also assessed intermolecular interactions, ADMET properties, quantum chemical analysis for the best complexes. [ABSTRACT FROM AUTHOR]- Published
- 2022
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