Identification of Lead Molecules against Multi-target of SARS-CoV-2 from Carica papaya L. through In-silico Method
Abstract
The efficacy of currently used vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is questionable since the virus is rapidly mutating. A single drug that can simultaneously act on multi-target at different stages of disease causing pathways is the best option to fight against it. The multi-target inhibitory activities of many phytochemicals have been reported. The present investigation was aimed to screen the multi-target inhibitory activity of 215 phytochemicals from Carica papaya L. against three targets of SARS-CoV-2 viz spike protein (SP), main protease (Mpro), RNA-dependent RNA-polymerase (RdRp) and a target from host, angiotensin-converting enzyme 2 (ACE-2) using the docking tool, AutoDock Vina in PyRx 0.8. The docked results with free energy of binding ≤ -6 kcal/mol were considered active/hit molecules. Of the 215 phytochemicals, 48 have binding energy ≤ -6 kcal/mol against all the targets. Further molecular interaction between the ligand and targets, pharmacokinetics and ADMET analysis of the top ranked five hits obtained against each target revealed that the compound hesperidin can be selected as the best lead since it has the least binding energy, admissible ADMET and a better binding score than the control drugs. Hesperidin has been used as an approved drug to treat vascular disease. Overall, results revealed that C. papaya is a rich source of phytochemicals with activity on multi-target of SARS-CoV-2 infection and multiplication in the human host.
Keywords:
ACE2, Mpro, RdRp, Carica papaya, Docking, Phytochemicals, SARS-CoV-2, Spike proteinDOI
https://doi.org/10.25004/IJPSDR.2023.150202References
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