Effectiveness of Natural Antioxidants against SARS-CoV-2? Insights from the In-Silico World

Abstract

The SARS CoV-2 pandemic has affected millions of people around the globe. Despite many efforts to find some effective medicines against SARS CoV-2, no established therapeutics are available yet. The use of phytochemicals as antiviral agents provides hope against the proliferation of SARS-CoV-2. Several natural compounds were analyzed by virtual screening against six SARS CoV-2 protein targets using molecular docking simulations in the present study. More than a hundred plant-derived secondary metabolites have been docked, including alkaloids, flavonoids, coumarins, and steroids. SARS CoV-2 protein targets include Main protease (MPro), Papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), Spike glycoprotein (S), Helicase (Nsp13), and E-Channel protein. Phytochemicals were evaluated by molecular docking, and MD simulations were performed using the YASARA structure using a modified genetic algorithm and AMBER03 force field. Binding energies and dissociation constants allowed the identification of potentially active compounds. Ligand-protein interactions provide an insight into the mechanism and potential of identified compounds. Glycyrrhizin and its metabolite 18-β-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp. The use of identified phytochemicals may help to speed up the drug development and provide natural protection against SARS-CoV-2.

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

“…The inhibitory effect of luteolin against the M pro is recently confirmed [146]. Fayyaz et al screened several flavonoids and identified three potentially active flavonoids, whose activities against SARS-CoV-2 M pro were in the order of rhodiolin > baicalin > silymarin based on their binding energy (−9.05, −8.85, −8.71 kcal/mol respectively) and dissociation constant (0.23, 0.33, 0.41 µm, respectively) using molecular docking and simulation studies [147]. Thioflavonol also inhibits Mpro [148] along with other flavonoids such as apigenin, daidzein, quercetin, kaempferol, luteolin, epigallocatechin, and kaempferol using molecular docking and simulation analysis [104].…”

“…On the other hand, naringin inhibits the spike glycoprotein more effectively with binding energy −9.8 kcal/mol compared to standard drug dexamethasone with the binding energy of −7.9 kcal/mol [156]. Fayyaz et al described potentially active flavonoids, whose activities against SARS-CoV-2 spike protein were in the order of rhodiolin > hesperidin (with active site 1) > hesperidin (with active site 2) > silyhermin based on their binding energy (−8.68, −8.53, −8.18, −8.05 kcal/mol, respectively) and dissociation constant (0.43, 0.56, 1.01, 1.25 µm respectively) [147]. The authors showed that hesperidin could bind to two different active sites on the spike glycoprotein with different binding energies.…”

“…Potentially active flavonoids, whose activities against SARS-CoV-2 PL Pro were in the order of baicalin > hesperidin > naringen > flemiflavanone D > Euchresta flavanone A on the basis of their binding energy (−10.82, −10.61, −10.17, −10.07, −9.95 kcal/mol, respectively) and dissociation constant (0.01, 0.02, 0.04, 0.04, 0.05 µm, respectively) using molecular docking and simulation studies [147]. The active site residues of PL Pro , which are found common with almost all the flavonoids were Lys157, Leu162, Gly163, Asp164, and Glu167, and therefore, all these residues are critical for the ligand interaction.…”

“…Shawan et al identified luteolin as a potential inhibitor of ACE2 with the binding energy of −10.1 kcal/mol, which is very close to the binding energy of FDA-approved remdesivir (−10.0 kcal/mol) [158]. Fayyaz et al identified three potentially active flavonoids against SARS-CoV-2 RdRp were in the order of hesperidin > baicalin > naringen based on their binding energy (−9.53, −9.01, −8.54 kcal/mol, respectively) and dissociation constant (0.1, 0.25, 0.55 µm, respectively) using molecular docking and simulation studies [147].…”

Antiviral Effects of Some Flavonoids on SARS-CoV-2

“…Several in silico studies suggested that flavonoids such as EGCG, hesperidin, oleuropein, and myricetin could be used as an alternative therapy for SARS-CoV-2 (Peterson, 2020;Khaerunnisa et al, 2020;Meneguzzo et al, 2020;Adem et al, 2020;Rehman MFu et al, 2021). Considering the promising results of the in silico studies, the potential therapeutic and prophylactic effects of plant-isolated natural flavonoids should be further investigated by in vitro studies to reveal their efficiency.…”