Molecular Screening of Aconitum Heterophyllum Identifies Potential Inhibitors of Typhoid Fever – Target Typhoid – 1,3- Dehydroquinate Dehydratase

Abstract

Background: Typhoid fever is a gram- negative bacterial infection caused by the bacterium called Salmonella typhi, a rod-like shaped pathogen. Salmonella typhi is both food-born and water-born pathogen. Developing nations exhibit a higher incidence of typhoid fever as a result of inadequate sanitation practices and incorrect use of antibiotics, hence fostering the emergence of drug resistance in the microorganisms known as bacteria Salmonella typhi. The enzyme "Typhoid-1, 3-dehydroquinate dehydratase" plays a crucial role in the biosynthesis of aromatic amino acids, particularly in the shikimate pathway. The shikimate pathway is accountable for the biosynthesis of aromatic amino acids, namely tyrosine, phenylalanine, and tryptophan.

Aim & Objective: The present study, we retrieved 3 bioactive Compounds such as Aconitine, Anthorine, Hypaconitine which inhibit the target enzyme Typhoid- 1,3- dehydroquinate dehydratase may act as a potential therapeutic agent for management of typhoid fever.

Materials and methods: Docking simulations were performed by using the Lamarckian genetic algorithm (LGA) and the Solis & Wets local search method. Initial position, orientation, and torsions of the ligand molecules were set randomly.

Results: Binding of phytocomponents with the core amino acids (His 143 and Lys-170) of the target Typhoid- 1, 3- dehydroquinate dehydratase by forming hydrogen bond will hinder the function of the enzyme and thereby inhibits biosynthesis of aromatic amino acids essential for the survival of the pathogen S. Typhi.

Conclusion: This characteristic renders the pathway a selective target for antibacterial drugs. Thereby phytocomponents which inhibit the target Typhoid-1,3-dehydroquinate dehydratase may act as a potential therapeutic agent for management of typhoid fever.