Introduction
Theaflavins belong to the class of polyphenols that are predominantly found in black tea. The major derivatives of theaflavins found in black tea are theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3′-gallate (TF2B), and theaflavin-3,3′-digallate (TF3). Theaflavin-3,3′-digallate (TF3) is a natural compound present in black tea and known to possess antiviral activity. This study had attempted to explore the potential role of TF3 in inhibiting various stages of the SARS-CoV-2 life cycle.
Methods
Molecular docking studies of TF3 along with positive controls was performed on eight different targets of SARS-CoV-2 followed by binding free energy (MM-GBSA) calculations. The docked complexes with favourable docking and binding free energy results were subjected to molecular dynamics (MD) simulation studies to assess the stability of the dock complex. Finally, TF3 and all the positive controls were taken for ADMET analysis.
Results
The docking and binding free energy results of TF3 was compared against the positive controls. TF3 showed the highest binding energy against all the targets and formed more stable interactions for a longer duration on MD simulations with CLpro, RdRp, helicase and spike protein. Also, the promising in-silico ADMET profile further warrants the exploration of this compound through in-vitro and in-vivo methods.
Conclusion
Through this study, we tried to evaluate the role of theaflavin-3,3’-digallate on multiple targets of SARS-CoV-2, and the positive in-silico results which were obtained on various pharmacodynamic and pharmacokinetic parameters, give a ray of hope as a potential therapeutic drug to this rapidly spreading disease. The search for a curative therapy for SARS-CoV-2 is still ongoing. The favourable preliminary results of TF3 through in-silico analysis offers a ray of hope in ending this devasting pandemic.
Supplementary Information
The online version contains supplementary material available at 10.1007/s42250-022-00376-7.
Background:
Several phyto-chemicals have been identified and suggested as potential therapeutic options for hepatotoxicity management.
Objective:
To assess the hepatoprotective effect of scopoletin, a pure phyto-chemical, in carbon tetrachloride (CCl
4
)-induced hepatotoxicity model in Wistar rats.
Methods:
Thirty-six rats in total, six in each group, were utilized in this study. Animals in group 1 received normal saline; those in group 2 received carbon tetrachloride in olive oil (0.5 ml/kg, i.p. in ratio 1:1); those in groups 3, 4, and 5 received oral scopoletin (1 mg/kg, 5 mg/kg, 10 mg/kg dose-wise groups); and those in group 6 received N-acetyl cysteine (NAC) 150 mg/kg. Blood sampling was performed on day -3, day 1, and day 7 of the CCl
4
administration. Rats were sacrificed on day 7 of the experiment for histological examination and oxidative stress measurement of the liver.
Results:
The 5 mg/kg scopoletin group showed a maximum reduction in AST levels [727.33 ± 29.15 in medium dose (MD) group vs 1526.66 ± 60.72 in the experimental control (EC) group (
P
< 0.001) and ALT levels of 532.66 ± 24.23 in MD group vs 894.83 ± 52.47 in EC (
P
< 0.01)]. The dose-dependent action was not observed with scopoletin doses. The protective effect of scopoletin was confirmed by MDA and GSH levels (
P
< 0.05) coupled with histo-pathological findings. In the present study, a reversible model of CCl
4
-induced hepatotoxicity was observed to get normalized in a week's time.
Conclusion:
The study confirms the hepatoprotective action of scopoletin in an acute model of hepatic injury with the putative anti-oxidant mechanism.
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