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Journal of Virology, June 2002, p. 6004-6015, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6004-6015.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Antiviral Effects of Pyrrolidine Dithiocarbamate on Human Rhinoviruses

Elisabeth Gaudernak,1 Joachim Seipelt,1 Andrea Triendl,1 Andreas Grassauer,2 and Ernst Kuechler1*

Institute of Medical Biochemistry, University of Vienna, Vienna Biocenter, A-1030 Vienna,1 Department of General Dermatology, University of Vienna Medical School, A-1090 Vienna, Austria2

Received 25 October 2001/ Accepted 22 March 2002

Human rhinoviruses (HRVs) are the predominant cause of the common cold. The frequency of HRV infections in industrial countries and the lack of effective therapeutical treatment underline the importance of research for new antiviral substances. As viral infections are often accompanied by the generation of oxidative stress inside the infected cells, several redox-active substances were tested as potential antivirals. In the course of these studies it was discovered that pyrrolidine dithiocarbamate (PDTC) is an extremely potent compound against HRV and poliovirus infection in cell culture. Besides the ability to dramatically reduce HRV production by interfering with viral protein expression, PDTC promotes cell survival and abolishes cytopathic effects in infected cells. PDTC also protects cells against poliovirus infection. These effects were highly specific, as several other antioxidants (vitamin C, Trolox, 2-mercaptoethanol, and N-acetyl-L-cysteine) are inactive against HRV infection. Synthesis of HRV proteins and cleavage of eucaryotic initiation factor 4G responsible for host cell shutoff of cellular protein synthesis are severely inhibited in the presence of PDTC.


* Corresponding author. Mailing address: Ernst Kuechler Institute of Medical Biochemistry, Bohrgasse 9/3, A-1030 Vienna, Austria. Phone: 43-1-4277-61610. Fax: 43-1-4277-9616. E-mail: kuechler{at}bch.univie.ac.at.


Journal of Virology, June 2002, p. 6004-6015, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6004-6015.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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