Cellular proteins (cyclin dependent kinases) as potential targets for antiviral drugs.
Several pharmacological inhibitors that are specific for cellular cyclin-dependent kinases (cdks) have recently been found to repress viral replication in vitro. Thus, replication of human cytomegalovirus, herpes simplex virus, and HIV-1 is repressed by pharmacological cdk inhibitors (PCIs). Replication of several other viruses requires cdks that are sensitive to PCIs. Interestingly, some of the PCIs that have antiviral activity in vitro are being tested in animal models and in human clinical trials as anti-cancer agents, showing little toxicity in vivo. Thus, PCIs have the potential to become antiviral drugs for clinical use. As PCIs repress viral replication by targetting cellular proteins, they would constitute a novel group of antivirals. They could be active against several unrelated viruses, and viral mutants that are resistant to conventional antiviral drugs, and could be used in combination with any antiviral drug that targets a viral protein. For viral diseases whose pathological mechanism requires cdks, such as virus-induced tumours, PCIs would repress both the aetiological agent and the pathogenic mechanism. In this review, the biochemical, cellular and antiviral activities of PCIs in vitro and their toxicity in vivo are discussed. Other cellular proteins that are required for viral replication could also be targets for new antiviral drugs.
Schang
L M
LM
Department of Biochemistry, University of Alberta, Heritage Medical Research Centre, Edmonton, Canada. luis.schang@ualberta.ca
D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000378:metabolism*; D013379:Substrate Specificity; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D018844:Cyclin-Dependent Kinases