Design and antiviral assessment of a panel of fusion proteins targeting human papillomavirus type 16.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
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

e0311137

Informations 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.

Auteurs

Chongzhi Bai (C)

Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Jinzhong, China.

Ruoyu Wang (R)

Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, China.

Qian Yang (Q)

Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, China.

Jianqing Hao (J)

School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China.

Qiming Zhong (Q)

Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, China.

Ruiwen Fan (R)

College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Jinzhong, China.

Pengcheng Han (P)

School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China.

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Classifications MeSH