IN SILICO?MOLECULAR DOCKING STUDY OF ANTIVIRAL PHYTOCHEMICAL COMPOUNDS AND SYNTHETIC DRUGS AS POTENTIAL BINDING COMPOUNDS WITH SARS-COV-2 PROTEINS

摘要

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing a respiratory disease called COVID-19 spread rapidly around the globe.In the present study, in silico molecular docking analysis was performed to identify natural or synthetic drug which directly inhibits the SARS-CoV-2.Initially, we conduct a depth literature search for compounds that had biologically confirmed antivirus activity.We performed a molecular docking study of 11 natural and 5 synthetic drugs against the SARS-CoV-2 spike protein, RNA-binding domain of nucleocapsid phosphoprotein and nsp9 RNA binding protein as the probable target proteins using iGemdock v.2.The selected antiviral compounds were cross-checked for listing in the pharmacology database and were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation for its effective oral administration.Based on the docking results, nafamostat mesylate exhibited a significantly strong interaction (-115.1kcal/mol) compared to the other compounds with the spike protein of coronavirus.However, it could not clinically apply due to its carcinogenic nature.However, delphinidin also efficiently bind (-94.4 kcal/mol) with spike protein.Additionally, plant-based compound cimicifugin has shown good binding efficacy with binding energy (-129.1 kcal/mol) to the RNA-binding domain of nucleocapsid phosphoprotein of SARS-CoV2.Among the others, daclatasvir and amentoflavone were found to interact with the nsp9 RNA binding protein of coronavirus (Binding energy: -123.5 Kcal/mol and -118 Kcal/mol respectively) besides violated 2 Lipinski’s rule.Moreover, silymarin a naturally-occurring bioflavonoid expressed a better binding affinity (-108.1 Kcal/mol) toward the nsp9 RNA binding protein.It has been concluded that delphinidin could bind efficiently with the spike protein and prevent the entry of coronavirus in the host cells.In addition, cimicifugin, and silymarin have potential in inhibiting the targeted replicative polyprotein required for the life cycle of coronavirus.These drugs could also be used in combination for antiviral treatment to fight particularly against SARS-CoV-2.However, further in vitro and in vivo research are necessary to explore its preventive therapeutic use for COVID-19.