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Updated: Aug 16, 2025

Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
06:03

Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16

Published on: July 15, 2019

8.0K

Molecular mechanism of antibody neutralization of coxsackievirus A16

Chao Zhang1,2, Caixuan Liu3, Jinping Shi1

  • 1CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Nature Communications
|December 21, 2022
PubMed

Insights

Two neutralizing monoclonal antibodies, 9B5 and 8C4, show promise against Coxsackievirus A16 (CVA16) infection. They work by blocking virus attachment and entry, offering potential for new CVA16 therapies.

Area of Science:

  • Virology
  • Immunology
  • Structural Biology

Background:

  • Coxsackievirus A16 (CVA16) is a significant cause of hand, foot, and mouth disease in children.
  • Currently, no specific vaccines or antiviral treatments exist for CVA16 infections.

Purpose of the Study:

  • To investigate the mechanisms of action and structural basis for neutralization by two CVA16-specific monoclonal antibodies (MAbs), 9B5 and 8C4.
  • To evaluate the in vitro and in vivo efficacy of these MAbs against CVA16.

Main Methods:

  • In vitro neutralization assays.
  • In vivo mouse models for CVA16 infection (prophylactic and therapeutic).
  • Cryo-electron microscopy (Cryo-EM) for structural analysis.
  • Epitope mapping and receptor interaction studies.

Main Results:

  • Both 9B5 and 8C4 MAbs demonstrated potent in vitro neutralization and significant prophylactic and therapeutic effects in a mouse model.
  • MAb 9B5 inhibits CVA16 attachment by blocking binding to heparan sulfate.
  • MAb 8C4 targets the post-attachment stage by interfering with SCARB2 interaction, crucial for virus uncoating.
  • Cryo-EM revealed distinct epitopes for 9B5 and 8C4 on the CVA16 capsid.
  • A combination of 9B5 and 8C4 MAbs prevented viral escape observed with individual antibodies.

Conclusions:

  • The study elucidates the distinct mechanisms of neutralization for 9B5 and 8C4 against CVA16.
  • These MAbs provide a foundation for developing effective antibody-based therapies and vaccines for CVA16.
  • The combination of MAbs offers a strategy to overcome viral resistance.

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