In Silico study for acyclovir, ganciclovir and its derivatives to fight the COVID-19: Molecular docking, DFT calculations, ADME and td-Molecular dynamics simulations

ABSTRACT

In the present work, we have designed acyclovir (A), ganciclovir (G) and derivative of hydroxymethyl derivative of ganciclovir (CH2OH of G, that is D) and investigated its potential against the Mpro of nCoV. Density functional theory (DFT) calculations of A, G and D were performed using Gaussian 16 on applying B3LYP under default condition to investigate the delocalization of electron density in their optimized geometry. Free energy of A, G and D were calculated in Hartree per particle. It can be seen that D has the least free energy. Further, the molecular docking of the A, G and D against the Mpro of nCoV was performed using iGemdock and the 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. For a better understanding of the inhibition of the Mpro of nCoV by A, G and D, temperature dependent molecular dynamics simulations were performed. Various trajectories like RMSD, RMSF, Rg and hydrogen bond were extracted and analyzed. The results of molecular docking corroborate the MD simulations and D could be a promising candidate against Mpro of nCoV.