Revelation of potent ES-62 activity of a hypothetical protein from Wuchereria bancrofti proteome by in-silico based characterization and functional annotation

Abstract

Lymphatic filariasis (LF) is a well-known disease caused primarily by the parasitic worm Wuchereria bancrofti, although other Filarioidea parasites, including Brugia malayi and Brugia timori, can also be responsible. These parasites can frequently affect the lymphatic system during their microfilariae stage. These parasites often produce numerous excretory-secretory (ES) products that can modulate or impede the activities of diverse immune system cells. Thus, this study utilized computational characterization and functional annotation to assess the impact of a hypothetical protein from Wuchereria brancrofti, specifically its role as an ES-62 product. The analysis of functional domain annotation indicates that the hypothetical protein shares functional domains comparable to those found in ES-62 (Zinc-binding metallopeptidase family protein). Additionally, the hypothetical protein has significant sequence similarities (73.83 %) with the ES-62 of Acanthocheilonema viteae, as shown by the multiple sequence alignment and phylogeny analyses. Furthermore, the hypothetical protein's secondary and tertiary structure and its tertiary model structure's quality possess an acceptable standard quality (Z-score of −9.45). Moreover, the molecular docking study demonstrates that the hypothetical protein shows a significant affinity for the TLR-4 receptor (center energy score of −1145.9 and the lowest energy score of −1096.5), a finding that is subsequently confirmed by normal mode analysis. These in silico findings suggest that the observed hypothetical protein could aid in studying filarial infection and developing pharmaceuticals to treat lymphatic filariasis.