Computational design of immunogenic peptide constructs comprising multiple human leukocyte antigen restricted dengue virus envelope epitopes

Abstract

Dengue virus (DENV) is endemic in 100 countries with the ability to impact nearly 50% of world population. DENV envelope (E) protein is responsible for viral attachment to host cells and has been target of various countermeasure development efforts. The current study focuses on a consensus computational approach to identify cross-reactive, immunogenic DENV-2 E peptides displaying promiscuity with a wide array of human leukocyte antigen (HLA) molecules. Four conserved peptides (FP-1, FP-2, FP-3 and FP-4) containing multiple CD8 + and CD4 + T cell epitopes were identified by employment of various immunoinformatics tools. FP-1, FP-2, FP-3 and FP-4 were estimated to bind with 227, 1787, 1008 and 834 HLA alleles, respectively. Root mean square deviation (RMSD) values obtained by molecular docking (CABS-Dock) with 20 HLA alleles (10 each of HLA classes I and II) resulted into comparable RMSD values of identified epitopes with native peptides, which represents the natural presentation of epitopes to HLA molecules. These peptides were also found to be part of previous experimentally validated immunogenic peptides. Further, a dengue immunogenic peptide construct was generated by linking the four peptides, an adjuvant and a 6Â histidine tag. The construct showed strong binding and stability with Tolllike receptor. Collectively, these results provide strong evidence in the support of the immunogenic potential of the dengue immunogenic peptide construct.

Designing a Conserved Immunogenic Peptide Construct from the Nucleocapsid Protein of Puumala orthohantavirus

“…Docking scores of most of the epitopes and peptides were found to be higher than or in the range of scores of naturally bound peptides, indicating the favorable presentation of peptides to HLA class I and II MHC to activate T cell immune response. The result is in agreement with previous studies on peptide-HLA interactions of Dengue [17]. Ismail and colleagues [23] also identified experimentally determined epitopes from the ViPR database and demonstrated their interaction with HLA molecules.…”

“…All three peptides displayed lower coverage for North America. There are similar studies [17,61] where the population coverage for some peptides was shown to be lower in North America than in other continents. The population coverage of peptides could be limited due to the absence of orthohantavirus-bindingdominant HLA alleles in North America in the peptides selected in our study.…”

“…In recent years, significant progress has been made in identifying potentially immunogenic peptides using the immunoinformatic approach, which has shown promising results in various experimental systems [15]. Various immunoinformatic methods were employed to identify immunogenic peptides containing multiple epitopes of SARS-CoV-2 [16], DENV [17], Ebola virus [18], H1N1 influenza virus [19,20], CanineCV [21], Zika virus [22], and hantavirus [23]. Computational identification of immunogenic peptides of Zika virus, SARS-CoV-2, Hantaan virus, and influenza virus has yielded favorable results in several experimental investigations [24][25][26].…”

Peptide‐Enabled Thrombus‐Targeting Nanoparticles for Highly Effective Targeted CT Imaging and Eradication of Thrombi

“…Further, the CABS‐Docking network server was used to simulate the interaction between thrombus‐binding peptides and fibrin. [ 16,54 ]…”

“…Further, the CABS-Docking network server was used to simulate the interaction between thrombus-binding peptides and fibrin. [16,54] The Synthesis of Bi Nanoparticles (NPs): Bi NPs were prepared from Bi(NO 3 ) 3 •5H 2 O by high temperature vacuum method. [55] Bi(NO 3 ) 3 •5H 2 O of 970 mg were dissolved in 1-dodecanethiol in a three-neck flask with magnetic stirring.…”