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Grafting Methionine on 1F1 Ab Increases the Broad-Activity on HA Structural-Conserved Residues of H1, H2, and H3 Influenza a Viruses
- Source :
- Evolutionary Bioinformatics, Vol 17 (2021), Evolutionary Bioinformatics
- Publication Year :
- 2021
- Publisher :
- SAGE Publications, 2021.
-
Abstract
- A high level of mutation enables the influenza A virus to resist antibiotics previously effective against the influenza A virus. A portion of the structure of hemagglutinin HA is assumed to be well-conserved to maintain its role in cellular fusion, and the structure tends to be more conserved than sequence. We designed peptide inhibitors to target the conserved residues on the HA surface, which were identified based on structural alignment. Most of the conserved and strongly similar residues are located in the receptor-binding and esterase regions on the HA1 domain In a later step, fragments of anti-HA antibodies were gathered and screened for the binding ability to the found conserved residues. As a result, Methionine amino acid got the best docking score within the −2.8 Å radius of Van der Waals when it is interacting with Tyrosine, Arginine, and Glutamic acid. Then, the binding affinity and spectrum of the fragments were enhanced by grafting hotspot amino acid into the fragments to form peptide inhibitors. Our peptide inhibitor was able to form in silico contact with a structurally conserved region across H1, H2, and H3 HA, with the binding site at the boundary between HA1 and HA2 domains, spreading across different monomers, suggesting a new target for designing broad-spectrum antibody and vaccine. This research presents an affordable method to design broad-spectrum peptide inhibitors using fragments of an antibody as a scaffold.
- Subjects :
- drug design
medicine.drug_class
Antibiotics
lcsh:Evolution
Hemagglutinin (influenza)
medicine.disease_cause
03 medical and health sciences
chemistry.chemical_compound
conserved residues
antibody
lcsh:QH359-425
Genetics
medicine
Influenza A virus
broad-spectrum
hemagglutinin
Ecology, Evolution, Behavior and Systematics
Original Research
030304 developmental biology
peptide inhibitor
0303 health sciences
Mutation
Methionine
biology
Chemistry
030302 biochemistry & molecular biology
Influenza a
Grafting
grafting
Virology
Computer Science Applications
biology.protein
Antibody
Subjects
Details
- ISSN :
- 11769343
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Evolutionary Bioinformatics
- Accession number :
- edsair.doi.dedup.....5af4b5f4fc5ba6d2275d0415f7086d8d