Strategy to Configure Multi-epitope Recombinant Immunogens with Weightage on Proinflamatory Response using SARS-CoV-2 Spike Glycoprotein (S-protein) and RNA-dependent RNA Polymerase (RdRp) as Model Targets

-

Research Article by: Nilesh Barman1, Arkajit De1, Joydeep Paul1, Srijan Haldar3, Arijit Bhattacharya2* and Kuntal Pal1*

Abstract

Development of a suitable recombinant peptide vaccine against pathogens requires designing of effective immunogenic polypeptide taking various aspects and complexity of immune-response into consideration. Implementing SARS-CoV-2 spike glycoprotein (S-protein) and RNA-dependent RNA polymerase (RdRp) as model targets, in this study, we outline and assess a strategy for in silico recombinant vaccine designing. After mapping the linear B-cell epitopes and MHC1-binding T-cell epitopes six epitopes were sorted from each of the proteins on the basis of extent of residue-conservancy among three types of coronaviruses namely SARS-CoV-2, SARS-CoV and MERS-CoV. Each of the selected epitopes were profiled for their pro-inflammatory potential through molecular docking analysis with surface bound Toll-like receptors, namely TLR2, TLR4 and TLR5. Based on a custom scoring function, the epitopes were ranked for highest and least pro-inflammatory potential. Segments of Spike and RdRp harboring such epitopes were combined using linkers to design immunogenic recombinant polypeptide. Antigenicity and allergenicity of each of the combination was scored; and the best fitting one was docked against TLR2, TLR4 and TLR5 for assessing pro-inflammatory potential. Codon optimization and in silico cloning in expression vector indicated that the designed peptide can be satisfactorily expressed in bacteria, reinforcing the viability of the strategy in identification and designing of potential immunogens.

Keywords

Spike glycoprotein, RNA-dependent RNA polymerase, Epitopes, Toll-like receptor, Combinatorial multi-epitope vaccine

Full Length Article: 10.22207/JPAM.16.1.17 

Comments

Post a Comment

Popular posts from this blog

Cryo-EM structure of the flagellar MS ring with FlgB-Dc loop and FliE-helix 1 from Salmonella (PDB ID: 7E81)

-
Image
Cryo-EM structure of the flagellar MS ring with FlgB-Dc loop and FliE-helix 1 from Salmonella (PDB ID: 7E81) The bacterial flagellar motor is a supramolecular protein machine that drives rotation of the flagellum for motility, which is essential for bacterial survival in different environments and a key determinant of pathogenicity. The detailed structure of the flagellar motor remains unknown. Here we present an atomic-resolution cryo electron microscopy (cryo-EM) structure of the bacterial flagellar motor complexed with the hook, consisting of 175 subunits with a molecular mass of approximately 6.3 MDa. The structure reveals that 10 peptides protruding from the MS ring with the FlgB and FliE subunits mediate torque transmission from the MS ring to the rod and overcome the symmetry mismatch between the rotational and helical structures in the motor. The LP ring contacts the distal rod and applies electrostatic forces to support its rotation and torque transmission to the hook. This wo
Read more

Biotechnology and its scopes

-
Image
The word 'Biotechnology' turned into first coined with the aid of using Karl Ereky in 1919. HE became additionally referred to as the 'Father of Biotechnology'. Biotechnology is described as the field of study that carries out both biological and technological chronological data that makes use of dwelling organisms and their derivatives for the production and development of products ranging from healthcare medicine to biofuels. Biotechnology is broadly classified into 10 categories according to their color codes and different sectors: A.      Medical Biotechnology, Human Health & Diagnostics   B.      Food Biotechnology and Nutritional Science   C.      Marine Biotechnology and Aquaculture Technology   D.     Agricultural Biotechnology, Environmental Biotechnology and Plant   Biotechnology   E.      Desert Biotechnology   F.       Bioterrorism, Biowarfare, Biocrimes, Anticrop Warfare   G.      Patents, Publications, Inventions, IPRs   H.      Gene-Based Bioindustri
Read more