CHLOROQUINE A POTENTIAL DRUG CANDIDATE FOR THE MANAGEMENT OF SNAKE BITE: A STRUCTURE BASED VIRTUAL SCREENING FOR MULTI-TARGET PROFILING

Abstract

Background: Considering the diversity in the pharmacological actions of chloroquine, it is likely that other potential mechanisms may exist in its action against other targets. Anti-snake-venom treatment is very expensive, out of reach and have several adverse effects because of the foreign protein involved, hence need for a cheaper, safer, readily available and more effective drug. Materials and Methods: PASS ONLINE target identification, molecular docking and pharmacophore modelling approach were employed in the structure based virtual screening against multiple snake venom proteins. Results: Six (6) snake venom proteins were selected from the PASS online screening software as potential targets for chloroquine; snake acetylcholinesterase, snake venom cardiotoxin, interferon 2A, tumor necrosis factor alpha, snake hemorrhagic metalloproteinase and snake phosphodiesterases. Chloroquine demonstrated excellent binding affinities (when compared to the co-crystalized ligands) against the six snake venom proteins. Additionally, it fits into the active pockets of the six targets. Again, chloroquine interacts with the amino acid residues of the snake venom proteins at its pharmacophore site. These findings showed the ability of chloroquine to effectively bind to these targets thereby inhibiting their effects. Conclusion: Though several studies have attempted to repurpose chloroquine for other indications. This study was the first to predict the activity of chloroquine against snake venom targets.