Identification of lead compounds with anti-cobra venom activity in common spices through in silico methods

Abstract

Snake bite envenomation a major neglected tropical disease, s a medical emergency in 21st century. Antisnake venom therapy/ the only specific antidote to snake venom has many limitations and side effects. To overcome the backdrops, discovery of novel faster and better alternative drug is necessary. Since time immemorial several herbal remedies have been used against snake bite by traditional healers. The present study aims to scientifically validate the efficacy of phytochemicals reported from three spice plants of Kerala namely allium cepa L., capsicum fruitescens L., cinnamomum Zeylanicum Blume and piper nigrum L., against selected 14 cobra venom toxic proteins using in silico approaches. Total 560 phytochemicals were screened against the target toxic proteins. The docked structures having free energy of binding less than-5 kcal/mol were selected as best hits and further analysis were done with the parameters such as hydrogen bonds, hydrophobic interaction, inhibition constant and lipinski’s rule of five. Comparative analysis of hits from total phytochemicals was done using DST method. The Results revealed that all the spices studied possess effective small molecules of drug value and antidote activity with varying level of binding affinity to the target venom proteins. A total of 26 leads were resulted by the study. Among theme curcuminoid, Beta sitosterol and Beta cubebine showed highly potential antitoxic effects. Cinnamomum Zeylanicum with five active lead molecules that together inhibits all the toxic venomprotein is the best antidote spice among the four subjected for the study. Piper nigrum with 9 antidote lead molecules that inhibit all the toxic proteins of snake venom ranked second. The study greatly substantiates the traditional knowledge of the antidote activity of the spices of Kerala. Further in vitro & in vivo studies and preclinical/ clinical trials are essential for the development of drugs out of these leads.