Kinetics of thermal denaturation of human rhinoviruses in the presence of anti-viral capsid binders analyzed by capillary electrophoresis

Electrophoresis
V M OkunE Kenndler

Abstract

In vivo, the icosahedral capsid of human rhinoviruses undergoes well-defined transitions during the infection pathway. Native virus, sedimenting at 150S, is converted to subviral particles with a sedimentation coefficient of 135S, which have lost the innermost capsid protein VP4. Upon release of the genomic RNA empty 80S capsids remain. Similar structural modifications are observed in vitro upon exposure to low pH and/or elevated temperature. Virions are stabilized against these transitions by various antiviral compounds, which bind to a hydrophobic pocket in the capsid protein VP1. Using capillary electrophoresis the kinetics of viral decay in the presence of such hydrophobic drugs was investigated. Assuming first-order kinetics, the increase of the time constant reflects the extent of stabilization. Exposure of the virions to 55 degrees C after presaturation with the antivirals increased the time constants (as compared to native virus) by a factor of 8-30, from a few minutes to several ten minutes. Denaturation of the stabilized capsid gave rise to heterogeneous material rather than to defined subviral particles. This was confirmed by electron microscopy and indicates that the structural modification of the virus follows a ki...Continue Reading

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Citations

Nov 21, 2008·Journal of Pharmaceutical and Biomedical Analysis·Iuliana OitaYvan Vander Heyden
Sep 10, 2008·Journal of Chromatography. a·Kurt BrorsonDouglas D Frey
Nov 17, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Victor U WeissErnst Kenndler
Jul 12, 2007·Journal of Separation Science·Leopold KremserErnst Kenndler
Dec 23, 2008·Electrophoresis·Leopold KremserErnst Kenndler
Oct 10, 2014·Journal of Separation Science·Hadewych HalewyckBart Rombaut
Aug 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jiri WaldMichaela Schmidtke
May 28, 2009·Analytical Chemistry·Michael JenikFranz L Dickert

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