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The effect of amantadine on an ion channel protein from Chikungunya virus

Debajit Dey1, Shumaila Iqbal Siddiqui2, Prabhudutta Mamidi3

  • 1Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, India.

Plos Neglected Tropical Diseases
|July 25, 2019
PubMed

Insights

Chikungunya virus 6K protein forms an ion channel in host cell membranes, crucial for viral replication. Amantadine effectively inhibits this channel and CHIKV infection, suggesting 6K as a therapeutic target.

Area of Science:

  • Virology
  • Molecular Biology
  • Membrane Biophysics

Background:

  • Viroporins are viral proteins forming channels in host membranes, essential for viral lifecycle.
  • The 6K protein of Chikungunya virus (CHIKV) is a suspected viroporin but remains poorly understood.

Purpose of the Study:

  • To characterize the CHIKV 6K protein's function and membrane association.
  • To investigate CHIKV 6K as a potential therapeutic target.

Main Methods:

  • Electrophysiology to study ion channel activity.
  • Confocal and electron microscopy for cellular localization.
  • Molecular dynamics simulations for mechanistic insights.

Main Results:

  • CHIKV 6K forms an ion channel, primarily localized to endoplasmic reticulum membranes.
  • Amantadine inhibits CHIKV 6K ion channel activity.
  • Amantadine effectively inhibits CHIKV infection in cell cultures.

Conclusions:

  • CHIKV 6K is a functional viroporin essential for CHIKV replication.
  • CHIKV 6K represents a promising therapeutic target.
  • Amantadine and derivatives show potential for CHIKV treatment.

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