Essential proteins and possible therapeutic targets of Wolbachia endosymbiont and development of FiloBase--a comprehensive drug target database for Lymphatic filariasis

Abstract

Lymphatic filariasis (Lf) is one of the oldest and most debilitating tropical diseases. Millions of people are suffering from this prevalent disease. It is estimated to infect over 120 million people in at least 80 nations of the world through the tropical and subtropical regions. More than one billion people are in danger of getting affected with this life-threatening disease. Several studies were suggested its emerging limitations and resistance towards the available drugs and therapeutic targets for Lf. Therefore, better medicine and drug targets are in demand. We took an initiative to identify the essential proteins of Wolbachia endosymbiont of Brugia malayi, which are indispensable for their survival and non-homologous to human host proteins. In this current study, we have used proteome subtractive approach to screen the possible therapeutic targets for wBm. In addition, numerous literatures were mined in the hunt for potential drug targets, drugs, epitopes, crystal structures, and expressed sequence tag (EST) sequences for filarial causing nematodes. Data obtained from our study were presented in a user friendly database named FiloBase. We hope that information stored in this database may be used for further research and drug development process against filariasis. URL: http://filobase.bicpu.edu.in.

Figure 1. Schematic representation of the various steps involved to identify the potential therapeutic targets and vaccine targets of wBm through extensive proteome subtractive approached.

Figure 2. Architecture of the FiloBase database.

Figure 3. The snapshot of the “Home Page” and “Result Page” of the FiloBase.

(a) Navigation window: It includes direct link to the various classified data in a single click, (b) Query search through text query, (c) List of potential drugs for Wolbachia endosymbiont, (d) Summary tab of the potential drug targets: It consists brief information about the therapeutic target, (e) Sequence tab: it contains the sequence and chain information of target protein, (f) Model verification tab: It contains model verification results obtained from PROCHECK, ERRAT and PROVE, (g) 3D structure tab: It contains the 3D modelled structure of the target protein with their active site pockets and (h) KEGG tab: It contains the graphical output of KEGG pathways if available.