&lt;i&gt;In silico&lt;/i&gt; antigenic site evaluation and antiviral therapy against dengue serotypes

Pratap Parida,Priyadarshini Deka,Brajesh Shankar,R.N.S Yadav

doi:10.3329/bjp.v9i1.17583

<i>In silico</i> antigenic site evaluation and antiviral therapy against dengue serotypes

Pratap Parida, Priyadarshini Deka + Show 2 more

Open Access

https://doi.org/10.3329/bjp.v9i1.17583

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Abstract

Nonstructural protein 3 (NS3) constitute protease, helicase and polymerase that are essential for dengue virus replication. The aim of the present study is to block the replication of the virus by targeting the NS3 Protein. The retrieved sequences of NS3 protein from National Centre for Biotechnology information shows that the antigenic sites of the protein are highly variable in all the four serotypes of dengue virus (DENV) i.e. DENV I, DENV II, DENV III and DENV IV. DENV III found to be most distantly related serotype among all the serotypes studied using UPGMA method. The 3D structure of NS3 protein was modeled using homology modeling by MODELLER 9v8. Evaluation of the constructed NS3 protein models were done by PROCHECK, WhatIf using Exome Horizon. The derived compounds of mycophenolic acid and ribavirin were docked as ligands to the constructed models of NS3 protein using AutoDock 4.2 for Protein-ligand interaction study.

Highlights

Dengue disease, caused by dengue virus infection which is found to be an endemic in over 100 countries (Brinkworth et al, 1999)
The antigenic sites analyzed from all the serotypes were found to be highly variable
It is observed that the amino acids present at the site producing highest scores were found to be A, P, V, C, G and Q for dengue virus (DENV) I

Summary

Introduction

Dengue disease, caused by dengue virus infection which is found to be an endemic in over 100 countries (Brinkworth et al, 1999). Every step in the life cycle of the dengue virus is a potential target for inhibiting viral replication (Qi et al, 2008). We assessed the ability of myco -phenolic acid (MPA) and ribavirin (RBV), drug currently used as an immunosuppressive agent, to inhibit dengue virus antigen expression, RNA replication, and virus production (Diamond et al, 2012; Allison et al, 1993; Koff et al, 1983; Conner et al, 1984). The aim of this study was to examine the mutation in antigenic site of dengue virus and the antiviral action of mycophenolic acid (MPA) and ribavirin (RBV) on NS3 proteins DENV I-IV determining the best drug that can be most active against the virus from the binding energy and the pocket which fits the drug

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