Small molecules targeting coxsackievirus A16 capsid inactivate viral particles and prevent viral binding

Chien Ju Lin, Ching Hsuan Liu, Jonathan Y. Wang, Chun Ching Lin, Yi Fang Li, Christopher D. Richardson, Liang Tzung Lin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Coxsackievirus A16 (CVA16) is an etiologic agent of hand, foot, and mouth disease (HFMD) that affects young children, and although typically self-limited, severe complications, and fatal cases have been reported. Due to the lack of specific medication and vaccines against CVA16, there is currently a need to develop effective antivirals to better control CVA16 infections in epidemic areas. In this study, we identified the tannins chebulagic acid (CHLA) and punicalagin (PUG) as small molecules that can efficiently disrupt the CVA16 infection of human rhabdomyosarcoma cells. Both compounds significantly reduced CVA16 infectivity at micromolar concentrations without apparent cytotoxicity. A mechanistic analysis revealed that the tannins particularly targeted the CVA16 entry phase by inactivating cell-free viral particles and inhibiting viral binding. Further examination by molecular docking analysis pinpointed the targets of the tannins in the fivefold axis canyon region of the CVA16 capsid near the pocket entrance that functions in cell surface receptor binding. We suggest that CHLA and PUG are efficient antagonists of CVA16 entry and could be of value as antiviral candidates or as starting points for developing molecules to treat CVA16 infections.

Original languageEnglish
Article number162
JournalEmerging Microbes and Infections
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Enterovirus
Capsid
Virion
Coxsackievirus Infections
Tannins
Antiviral Agents
Molecular Docking Simulation
Hand, Foot and Mouth Disease
Rhabdomyosarcoma
Cell Surface Receptors
Vaccines

ASJC Scopus subject areas

  • Epidemiology
  • Parasitology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Infectious Diseases
  • Virology

Cite this

Small molecules targeting coxsackievirus A16 capsid inactivate viral particles and prevent viral binding. / Lin, Chien Ju; Liu, Ching Hsuan; Wang, Jonathan Y.; Lin, Chun Ching; Li, Yi Fang; Richardson, Christopher D.; Lin, Liang Tzung.

In: Emerging Microbes and Infections, Vol. 7, No. 1, 162, 01.12.2018.

Research output: Contribution to journalArticle

Lin, Chien Ju ; Liu, Ching Hsuan ; Wang, Jonathan Y. ; Lin, Chun Ching ; Li, Yi Fang ; Richardson, Christopher D. ; Lin, Liang Tzung. / Small molecules targeting coxsackievirus A16 capsid inactivate viral particles and prevent viral binding. In: Emerging Microbes and Infections. 2018 ; Vol. 7, No. 1.
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