An antiviral compound that blocks structural transitions of poliovirus prevents receptor binding at low temperatures

A W Dove1, V R Racaniello

  • 1Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

Journal of Virology
|March 23, 2000
PubMed

Insights

WIN51711 drug inhibits poliovirus infectivity by blocking capsid uncoating. This antiviral drug

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • Picornavirus replication inhibitors, like WIN51711, are believed to prevent poliovirus infectivity.
  • These drugs are thought to bind the viral capsid, inhibiting structural transitions essential for uncoating.

Purpose of the Study:

  • To investigate the mechanism of WIN51711 antiviral activity.
  • To determine the role of capsid structural transitions in poliovirus binding to cellular receptors at reduced temperatures.

Main Methods:

  • Examined WIN51711 activity at temperatures below 37°C, where capsid flexibility is reduced.
  • Assessed the effect of WIN51711 on the binding of wild-type poliovirus and a poliovirus mutant to host cells.

Main Results:

  • WIN51711 inhibited wild-type poliovirus binding to cells at temperatures below 37°C.
  • The drug did not affect the binding of a poliovirus mutant known to undergo structural transitions more readily.
  • These findings indicate that poliovirus capsid structural changes are necessary for cellular receptor binding.

Conclusions:

  • Poliovirus capsid structural transitions are critical for cellular receptor interaction.
  • WIN51711's antiviral mechanism is dependent on the ability of the capsid to undergo these conformational changes.
  • The study provides insight into poliovirus entry mechanisms and potential antiviral targets.

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