Top Down Computational Approach: A Vaccine Development Step to Find Novel Superantigenic HLA Binding Epitopes from Dengue Virus Proteome

Dengue virus (DENV) is a major mosquito vector based human pathogenic flavivirus which is causing major threat worldwide, yet the availability of therapeutic treatment and several vaccines, still called for advance treatment and vaccine development. The present top down computational approach is a vaccine development step to find novel super antigenic HLA binding epitopes from DENV proteome. The approach used sequence based screening to find complete conserve and high population coverage, common epitopes among all DENV serotype. Propred and Immune Epitope Data Base were used for sequence based screening with recommended parameters. Among top 29 identified epitopes, five structural protein epitopes viz. (33)LQGRGPLKL(41), (249)VVVLGSQEG(257), (172)LVGIVTLYL(180), (146)MKILIGVVI(154), (72)YIIVGVEPG(80) and one nonstructural protein epitope (18)LKNDIPMTG(26) were showed high conserve nature and high population coverage from complete DENV proteome. Further structure based study involving docking and molecular dynamic simulation to confirm stable behavior of HLA allele–peptide complex to give potent cell mediated immune response. Docking of epitope (72)YIIVGVEPG(80)–DRB1 0401 allele and epitope (33)LQGRGPLKL(41)–B*5101 allele complexes showed the best binding energy of − 7.71 and − 7.20 kcal/mol, respectively and stable binding pattern over the time window during molecular dynamic simulation. This computational approach resulted novel epitopes which can be used in the design and development of short epitope based vaccines as well as diagnosis tools for dengue infection.