From genome to drug targets: computational subtractive genomics reveals novel anti-filarial targets in Wuchereria bancrofti and identifies plant-based inhibitors of β-1,4-mannosyltransferase, a high-priority target.

Lymphatic filariasis (LF) is a mosquito-transmitted parasitic disease, which is a main concern in tropical and subtropical countries. LF is the second major cause of chronic and irreversible disabilities worldwide, which include lymphoedema, hydrocele, and elephantiasis. According to the World Health Organization (WHO), an estimated 882 million individuals across 44 countries were reported to be at risk of acquiring LF. The nematode Wuchereria bancrofti is the predominant pathogen which causes LF, accounting for approximately 90% of filarial infections. The drugs albendazole (ALB), ivermectin (IVM), and diethylcarbamazine (DEC) are currently used to treat LF, but they are not effective against microfilariae and are known to have an inability to reverse chronic conditions, produce adverse reactions, and have developed drug resistance due to prolonged use. Further scientific studies are necessary to discover and characterize potential drug targets in the genome of W. bancrofti, which would facilitate the development of novel therapeutic approaches. This study employs a subtractive genomics approach to identify potential anti-filarial drug targets from the genome of W. bancrofti. Our analysis revealed 12 targets of W. bancrofti, which were found to be involved in important metabolic pathways such as combating oxidative stress, amino acid and nucleotide metabolism, folate biosynthesis, and DNA repair. This article highlights the proposed drug targets and their potential role in the development of effective drugs against W. bancrofti. We also propose beta-1,4-mannosyltransferase (WbEGH), one among the 12 identified targets, as a priority target based on its sequence similarity with human proteins. Further, structure-based virtual screening identified five potent phytochemicals (IMPPAT ID: 9,896,047, 49,777,225, 13,888,122, 89,483-03-4, and 14,605,093) having a better affinity with WbEGH. Furthermore, experimental validation of these identified phytochemicals would lead towards an effective method for controlling Lymphatic Filariasis.