In silico investigations of the multi-targeted antiviral potential of small molecule phytochemicals of Nelumbo nucifera Gaertn. seed extracts against SARS-CoV-2 for therapeutics of COVID-19

ABSTRACT

The therapeutics of COVID-2 was significantly obtained from nutraceutical approaches based on traditional knowledges and long practices. The current study was aimed to investigate antiviral potential of small molecule phytochemicals of seeds of Nelumbo nucifera against the SARS-CoV-2 proteins. GC–MS analysis resulted in identifying 12 dominating small molecule phytocompounds from the seed extracts of the N. nucifera. Further, we selected RNA-dependent RNA polymerases (RdRps), spike protein, and M protein of SARS-CoV-2 as antiviral targets and performed in silico analyses, including protein docking (ligands), ADMET predictions, and molecular dynamics (MD). The studies revealed that the molecular interactions (protein–ligands) of three target proteins, namely, RdRp, spike protein, and M-protein, have significant binding energies with three different substrates, namely, 1-(8′-methylquinolin-2′-yl)-2,3,4-tri(methoxycarbonyl)-6-(1″,2″-di(methoxycarbonyl)vinyloxy)benzene (binding energy −5.84 kcal/mol) 2(1H)-pyrimidinone, 5-chloro-4,6-diphenyl (binding energy −6.60 kcal/mol), and nickel, [2,8,12,18-tetraethyl-3,7,13,17-tetramethyl-21H,23H-porphinato(2-)-N21,N22,N23,N24]-, (SP-4-1) (binding energy −7.02 kcal/mol), respectively. The ADMET predictions show significant pharmacokinetic profiles of the druggability of the three compounds of different targets. The pharmacokinetic activities critical to predicting stages of the drug development process are gastrointestinal absorption and brain access. The MD simulation showed that the systems were stable, referring to them as a potentially effective treatment for SARS-CoV-2. Therefore, a possible initiative has been taken to evaluate three potent small molecules of antiviral phytocompounds made from typically edible N. nucifera seed to support the nutraceutical approach to COVID-19 therapeutics. © 2022 The Authors. Food Frontiers published by John Wiley & Sons Australia, Ltd and Nanchang University, Northwest University, Jiangsu University, Zhejiang University, Fujian Agriculture and Forestry University.