Title: In silico studies support the anti-scrub typhus activity of the bioactive phytocompounds andrographolide and withanolide D
Abstract:
An obligate intracellular bacterium Orientia tsutsugamushi is the causative agent of a febrile disease, scrub typhus, which is endemic to Southeast Asia, including India, wherein there is a recent report on increased emergence of the disease in West Bengal state. The antibiotic treatment failure of scrub typhus prompted us to search for non-antibiotic plant-based therapeutics. Herein we have performed in silico molecular docking of two bioactive phytochemicals, andrographolide (from Andrographis paniculate; Family: Acanthaceae) and withanolide D (from Withania somnifera; Family: Solanaceae) along with a standard treatment, tetracycline against OtDUB (Orientia tsutsugamushi deubiquitylase) protein associated with Orientia tsutsugamushi infection and pathogenesis of scrub typhus. The compound withanolide D (binding energy: -10.2 kcal/mole) had higher affinity to OtDUB compared to tetracycline (binding energy: -9.1 kcal/mole) and andrographolide (binding energy: -8.4 kcal/mole). Both the phytocompounds, andrographolide and withanolide D obeyed Lipinski’s rule of without any violation, and both exhibited high GI absorption and no BBB permeation. The current study results signify the effectiveness and importance of the phytocompounds as non-antibiotic therapy for scrub typhus.
