Design and antiviral assessment of a panel of fusion proteins targeting human papillomavirus type 16.
Human papillomavirus 16
/ genetics
Humans
Recombinant Fusion Proteins
/ genetics
Molecular Docking Simulation
Papillomavirus Infections
/ virology
Female
Capsid Proteins
/ genetics
Antibodies, Neutralizing
/ immunology
Oncogene Proteins, Viral
/ immunology
Antiviral Agents
/ pharmacology
Single-Domain Antibodies
/ pharmacology
Antibodies, Viral
/ immunology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2024
2024
Historique:
received:
01
07
2024
accepted:
15
09
2024
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Cervical cancer ranks as the third most prevalent malignancy in women worldwide. The persistence of Human papillomavirus (HPV) infection stands out as the foremost risk factor for cervical cancer development. Among the numerous HPV subtypes, HPV16 infection emerges as the primary pathogenic determinant of cervical cancer. To date, no specific drugs have been approved. In this study, we engineered two high-affinity fusion protein targeting HPV16 L1 protein based on the alpaca-derived single-domain antibody 2C12 previously obtained in our laboratory. These two fusion proteins exhibited potent neutralizing activity against HPV16 pseudovirus with IC50 values of 7.8 nM and 6.5 nM, respectively. Molecular docking analysis revealed that 2C12 formed ten pairs of hydrogen bonds with HPV16 L1, among which Arg39 and Thr100 established multiple pairs of hydrogen bonds with HPV16 L1, indicating their crucial roles in antigen-antibody binding process. These structural and biological findings underscore the effective binding capacity of these fusion proteins to HPV16, leading to reduced viral load and providing valuable insights into therapeutic antibody and vaccine development against HPV 16 infection.
Identifiants
pubmed: 39453911
doi: 10.1371/journal.pone.0311137
pii: PONE-D-24-26930
doi:
Substances chimiques
Recombinant Fusion Proteins
0
Capsid Proteins
0
Antibodies, Neutralizing
0
Oncogene Proteins, Viral
0
Antiviral Agents
0
L1 protein, Human papillomavirus type 16
6LTE2DNX63
Single-Domain Antibodies
0
Antibodies, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0311137Informations de copyright
Copyright: © 2024 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.