Computational identification of a multi-peptide vaccine candidate in E2 glycoprotein against diverse Hepatitis C virus genotypes.
J Biomol Struct Dyn
; 41(20): 11044-11061, 2023 12.
Article
in En
| MEDLINE
| ID: mdl-37194293
ABSTRACT
Hepatitis C Virus (HCV) is estimated to affect nearly 180 million people worldwide, culminating in â¼0.7 million yearly casualties. However, a safe vaccine against HCV is not yet available. This study endeavored to identify a multi-genotypic, multi-epitopic, safe, and globally competent HCV vaccine candidate. We employed a consensus epitope prediction strategy to identify multi-epitopic peptides in all known envelope glycoprotein (E2) sequences, belonging to diverse HCV genotypes. The obtained peptides were screened for toxicity, allergenicity, autoimmunity and antigenicity, resulting in two favorable peptides viz., P2 (VYCFTPSPVVVG) and P3 (YRLWHYPCTV). Evolutionary conservation analysis indicated that P2 and P3 are highly conserved, supporting their use as part of a designed multi-genotypic vaccine. Population coverage analysis revealed that P2 and P3 are likely to be presented by >89% Human Leukocyte Antigen (HLA) molecules from six geographical regions. Indeed, molecular docking predicted the physical binding of P2 and P3 to various representative HLAs. We designed a vaccine construct using these peptides and assessed its binding to toll-like receptor 4 (TLR-4) by molecular docking and simulation. Subsequent analysis by energy-based and machine learning tools predicted high binding affinity and pinpointed the key binding residues (i.e. hotspots) in P2 and P3. Also, a favorable immunogenic profile of the construct was predicted by immune simulations. We encourage the scientific community to validate our vaccine construct in vitro and in vivo.Communicated by Ramaswamy H. Sarma.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatitis C
/
Hepacivirus
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
J Biomol Struct Dyn
Year:
2023
Document type:
Article
Affiliation country:
India