Epitope prediction and designing of receptor inhibitor of Dengue Envelope Protein: An in silico approach

Abstract

Background & objectives: Dengue virus (DENV) is the causative agent of dengue fever (DF) and dengue hemorrhagic fever (DHF). It has four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) based on their antigenic properties. Mostly, the immunogenic epitopes are present in the envelope (E) protein of the virus. Heparan sulfate (HS) acts as a receptor and interacts with the E protein of the virus thus facilitating the entry of dengue virus into human cells. This study focuses on epitope prediction on the E protein of the DENV serotype. The non-competitive inhibitors of HS were designed using bioinformatics. Methods: In the present study, epitope prediction of the E protein of DENV serotypes was performed using the ABCpred server and IEDB analysis resource. The interactions of HS and viral E proteins (PDB ID: 3WE1 and PDB ID:1TG8) were evaluated through AutoDock. Subsequently, non-competitive inhibitors were designed to bind the E protein of DENV better than HS. All the docking results were validated by re-docking the ligand-receptor complexes and superimposing them onto their co-crystallized complexes using AutoDock and visualizing them in Discovery Studio. Results: The result predicted B-cell and T-cell epitopes on the E protein of DENV serotypes. The designed HS ligand 1 (non-competitive inhibitor) demonstrated potential binding with the DENV E protein, thereby inhibiting HS-E protein binding. The re-docked complexes were superimposed entirely onto the native co-crystallized complexes (low root mean square deviation values), which validates the docking protocols. Interpretation & conclusion: The identified B-cell and T-cell epitopes of the E protein and non-competitive inhibitors of HS (ligand 1) could be used in the designing of potential drug candidates against the dengue virus. © 2023 Wolters Kluwer Medknow Publications. All rights reserved.