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Structure paper

TitleDiscovery and structural characterization of a therapeutic antibody against coxsackievirus A10.
Journal, issue, pagesSci Adv, Vol. 4, Issue 9, Page eaat7459, Year 2018
Publish dateSep 19, 2018
AuthorsRui Zhu / Longfa Xu / Qingbing Zheng / Yanxiang Cui / Shaowei Li / Maozhou He / Zhichao Yin / Dongxiao Liu / Shuxuan Li / Zizhen Li / Zhenqin Chen / Hai Yu / Yuqiong Que / Che Liu / Zhibo Kong / Jun Zhang / Timothy S Baker / Xiaodong Yan / Z Hong Zhou / Tong Cheng / Ningshao Xia /
PubMed AbstractCoxsackievirus A10 (CVA10) recently emerged as a major pathogen of hand, foot, and mouth disease and herpangina in children worldwide, and lack of a vaccine or a cure against CVA10 infections has ...Coxsackievirus A10 (CVA10) recently emerged as a major pathogen of hand, foot, and mouth disease and herpangina in children worldwide, and lack of a vaccine or a cure against CVA10 infections has made therapeutic antibody identification a public health priority. By targeting a local isolate, CVA10-FJ-01, we obtained a potent antibody, 2G8, against all three capsid forms of CVA10. We show that 2G8 exhibited both 100% preventive and 100% therapeutic efficacy against CVA10 infection in mice. Comparisons of the near-atomic cryo-electron microscopy structures of the three forms of CVA10 capsid and their complexes with 2G8 Fab reveal that a single Fab binds a border region across the three capsid proteins (VP1 to VP3) and explain 2G8's remarkable cross-reactivities against all three capsid forms. The atomic structures of this first neutralizing antibody of CVA10 should inform strategies for designing vaccines and therapeutics against CVA10 infections.
External linksSci Adv / PubMed:30255146 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 4.3 Å
Structure data

9600

6acu

EMDB-9600, PDB-6acu:
The structure of CVA10 virus mature virion
Method: EM (single particle) / Resolution: 3.4 Å

9601

6acw

EMDB-9601, PDB-6acw:
The structure of CVA10 virus procapsid particle
Method: EM (single particle) / Resolution: 4.0 Å

9602

6acy

EMDB-9602, PDB-6acy:
The structure of CVA10 virus A-particle
Method: EM (single particle) / Resolution: 3.4 Å

9603

6acz

EMDB-9603, PDB-6acz:
The structure of CVA10 virus A-particle from its complex with Fab 2G8
Method: EM (single particle) / Resolution: 4.3 Å

9604

6ad0

EMDB-9604, PDB-6ad0:
The structure of CVA10 mature virion in complex with Fab 2G8
Method: EM (single particle) / Resolution: 3.9 Å

9605

6ad1

EMDB-9605, PDB-6ad1:
The structure of CVA10 procapsid from its complex with Fab 2G8
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-9606:
The structure of CVA10 virus A-particle
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-SPH:
SPHINGOSINE / Sphingosine

Source
  • coxsackievirus a10
  • mus musculus (house mouse)
KeywordsVIRUS / CVA10 / Mature virion / Icosahedral / procapsid / A-particle / immune complex / neutralizing antibody / VIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM complex

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