In-silico comparison of inhibition of wild and drug-resistant Haemonchus contortus β-tubulin isotype-1 by glycyrrhetinic acid, thymol and albendazole interactions.

ABSTRACT: Haemonchus contortus is among the most prevalent pathogenic gastrointestinal nematodes that poses significant health issues in small ruminants. Control of Haemonchus contortus relies on benzimidazoles. However, most small ruminants have started showing benzimidazole resistance due to prolonged and intensive drug consumption It is postulated that single nucleotide polymorphism of specific amino acids, Phe200Tyr, Phe167Tyr and Glu198Ala in β-tubulin is the causal factor of this resistance. Hence, a plethora of alternative anthelmintic drug is currently being investigated. The present study intends to investigate in silico anthelmintic potential of glycyrrhetinic acid and thymol against wild and mutant β-tubulin protein of Haemonchus contortus. Based on binding energies obtained in docking studies using AutoDock 4.0, mutant β-tubulin at Phe200Tyr, Phe167Tyr and Glu198Ala illustrates insignificant changes in binding affinity of albendazole in comparison to the wild β-tubulin. However, glycyrrhetinic acid and thymol exhibited significantly greater binding affinities towards mutant β-tubulin in comparison to the albendazole-wild β-tubulin binding affinity. Hence, these phytocompounds can potentially inhibit both wild and mutant Haemonchus contortus β-tubulin polymerization. If established by in vitro and in vivo experiments, glycyrrhetinic acid could be an alternative anthelmintic compound, thus, further motivating the concept of reverse pharmacognosy. SUPPLEMENTARY INFORMATION: is available for this paper at 10.1007/s12639-020-01274-w. © Indian Society for Parasitology 2020.