Antiviral effects of pyrrolidine dithiocarbamate on human rhinoviruses.
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.
Gaudernak
Elisabeth
E
Institute of Medical Biochemistry, University of Vienna, Vienna Biocenter, A-1030 Vienna, Austria.
Seipelt
Joachim
J
Triendl
Andrea
A
Grassauer
Andreas
A
Kuechler
Ernst
E
D000998:Antiviral Agents / Q000494:pharmacology*; D002213:Capsid / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D017955:Poliovirus / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology*; D012229:Rhinovirus / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D013859:Thiocarbamates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid