Immunoinformatics based screening and characterization of potential epitopes for SARS and MERS coronaviruses

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Severe AcuteRespiratory Syndrome Coronavirus (SARS-CoV) are the causal coronaviruses forMiddle East Respiratory Syndrome (MERS) and Severe Acute RespiratorySyndrome (SARS) respectively. So far major MERS outbreaks have beenreported from Saudi Arabia (2013, 2014) and South Korea (2015). SARS isendemic in south China and is continuing to spread worldwide since the outbreakof year 2003, affecting human population of 37 countries till present. To addressthe urgent need for a MERS and SRAS vaccine, in the present study, we havedesign two multi-epitope vaccines (MEVs) composed of screened CTL and HTLepitopes from their respective proteomes. Both the MEVs also carry potential Bcell linear epitope overlapping regions, B cell discontinuous epitopes as well asthe IFN-and#947; inducing epitopes; hence both MEVs carry potential to elicit humoral aswell as cell mediated immune response. The chosen CTL and HTL epitopes werevalidated for their stable molecular interactions with their respective HLA class Iand II allele binders; moreover, the chosen CTL epitopes were also analyzed fortheir molecular interaction with the Transporter associated with antigenprocessing. Human and#946;-defensin 2 and and#946;-defensin 3 were used as adjuvant toenhance immune response of MERS MEVs, likewise the truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1)was utilized as adjuvant for SARS MEVs.The tertiary models for MERS andSARS MEVs were generated, refined, and docked with Toll-Like Receptors; theMEV-TLR complexes were further studied for their stable molecular interactionby molecular dynamics simulation. cDNA of MERS and SARS MEVs wereanalyzed and predicted to have high expression in mammalian host cell line(Human), hence they could be cloned and expressed for further in-vivo trials.Overall the present study proposes in-silico validated design of MERS and SARSMEVs composed of specific epitopes with potential to cause a high level of virus specific..........