An In Silico investigation for acyclovir and its derivatives to fight the COVID-19: Molecular docking,DFT calculations,ADME and td-Molecular dynamics simulations |
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Authors: | Madhur Babu Singh Pallavi Jain Jaya Tomar Vinod Kumar Indra Bahadur Dinesh Kumar Arya Prashant Singh |
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Affiliation: | 1. Department of Chemistry, Atma Ram Sanatan Dharma College, University of Delhi, New Delhi, India;2. Department of Chemistry, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Delhi NCR Campus, Modinagar, Uttar Pradesh, India;3. SCNS, Jawaharlal Nehru University, New Delhi, India;4. Department of Chemistry, Faculty of Natural and Agricultural Sciences, North-West University, South Africa;5. Department of Chemistry, Acharya Narendra Dev College, University of Delhi, New Delhi, India |
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Abstract: | In the present work, we have designed three molecules, acyclovir (A), ganciclovir (G) and derivative of hydroxymethyl derivative of ganciclovir (CH2OH of G, that is D) and investigated their biological potential against the Mpro of nCoV via in silico studies. Further, density functional theory (DFT) calculations of A, G and D were performed using Gaussian 16 on applying B3LYP under default condition to collect the information for the delocalization of electron density in their optimized geometry. Authors have also calculated various energies including free energy of A, G and D in Hartree per particle. It can be seen that D has the least free energy. As mentioned, the molecular docking of the A, G and D against the Mpro of nCoV was performed using iGemdock, an acceptable computational tool and the interaction has been studied in the form of physical data, that is, binding energy for A, G and D were calculated in kcal/mol. It can be seen the D showed effective binding, that is, maximum inhibition that A and G. For a better understanding for the inhibition of the Mpro of nCoV by A, G and D, temperature dependent molecular dynamics simulations were performed. Different trajectories like RMSD, RMSF, Rg and hydrogen bond were extracted and analyzed. The results of molecular docking of A, G and D corroborate with the td-MD simulations and hypothesized that D could be a promising candidate to inhibit the activity of Mpro of nCoV. |
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Keywords: | Molecular dynamics simulations Molecular docking DFT studies ADME Repurposing drugs Mpro of nCoV |
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