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Epitope Prediction and Designing of Receptor Inhibitor of Dengue Envelope Protein: an In-silico Approach
Gunjan Uttam, Ankita Kumari, Karuna Singh
Department of Zoology, Mahila Mahavidyalaya, Banaras Hindu University, Varanasi-221005, India
Correspondence Address:
Karuna Singh,
Department of Zoology, Mahila Mahavidyalaya, Banaras Hindu University, Varanasi-221005, India.
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/0972-9062.361168
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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 the bioinformatics approach.
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 RMSD 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.
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