The recent evolution of the SARS-like Coronavirus has ravaged the world. The deadly virus has claimed over millions of lives across the world and hence highlights the need to develop effective therapeutic drugs to contain the disease posed by this parasite. In this study, the inhibitory potential of fifty (50) dietary polyphenols against Coronavirus (SARS-CoV-2) main protease (Mpro) was conducted using the Autodock Vina Molecular docking tool. In the virtual screening process, the binding affinity of Remdesivir (-7.7 kcal/mol) currently used to treat COVID-19 patients was set as the cut-off value to screen out less probable inhibitors. Ellagic acid, Kievitone, and Punicalin were the only promising ligands with binding affinities (-8.9 kcal/mol, -8.0 kcal/mol and -7.9 kcal/mol respectively) lower than the set cut-off value. Furthermore, we validated Ellagic acid and Kievitone efficacy by subjecting them to molecular dynamics simulation and further stability was assessed at the molecular mechanics and quantum levels. The overall analysis indicates both compounds demonstrate higher stability and inhibitory potential to bind to the crucial His41 and Cys145 catalytic dyad of Mpro than the standard drug. However, further analysis of punicalin after evaluating its docking score was not conducted as the ligand pharmacokinetics properties suggests it could pose serious adverse effect to the health of participants in clinical trials. Hence, we employed a more safe approach by filtering out the compound during this study. Conclusively, while Ellagic acid and kievitone polyphenolic compounds have been demonstrated to be promising under this in silico research, further studies are needed to substantiate their clinical relevance.
10 January 2016 in British Journal of Medicine and Medical Research
Currently available synthetic drugs for management of diabetes mellitus have been reported to cause side effects, hence searches for safer, readily available and cheaper sources among medicinal plants. One hundred and thirty rats weighing average of 94g were used for the studies. In the first study, Azadirachta indica (AZI) was assessed for its hypolipidemic property, in the second AZI was assessed for its antihyperglycaemic potential while in the third study; it was assessed for its antidiabetic, antilipidemic and antioxidative properties. The potency of 2 different doses of AZI was compared with that of glibenclamide (a reference drug). AZI exhibited hypoglycemic, antihyperglycemic, antihyperlipidemic and antioxidative properties which were comparable to that of glibenclamide. Different doses of AZI reversed weight loss due to streptozotocin-induced diabetes mellitus. AZI extract caused increased synthesis of liver glycogen when compared with diabetic rats. Conclusively, antidiabetic property of AZI may imitate blood glucose regulatory action of insulin.
It is no longer news that a novel strain of coronavirus named SARS-CoV-2 is ravaging the health sector worldwide, several attempts have been made to curtail this pandemic via repurposing of old drugs but at the present, available drugs are not adequately effective. Over the year, plant phytochemicals are increasingly becoming an alternative source of an antimicrobial agent with a novel mechanism of action and limited side effects compared to synthetic drugs. Isolated saponins and tannins were evaluated for antiviral activity against SARS-CoV-2 Mpro via Molecular Docking and it was observed that a handsome number of the phytochemicals had binding affinity much better than Remdesivir, Dexamethasone, and N3 inhibitor which were used as the standard in this study. Further Investigation of drug-likeness, ADMET profile, and bioactivity of these phytochemicals revealed that binding affinity alone is not enough in the drug discovery process and that 4 hit compounds were identified as potential inhibitors of SARS-CoV-2Mpro. This preliminary study furnishes Ellagic acid, Arjunic acid, Theasapogenol B, and Euscaphic acid as potential inhibitors of SARS-CoV-2 Mpro with better pharmacokinetics and bioavailability compared to Remdesivir which is currently used compassionately.