Although targeting
viral proteins has lead to many successful
antiviral drugs, these
antivirals have certain limitations. They rapidly select for resistance, tend to be active against only a few related viruses and the
proteins of a pathogen must be characterized before such drugs can be developed. Consequently, a long period is required from the identification of a new pathogen to the development of relevant
antivirals, a major concern for emerging diseases. Cellular
proteins are now considered as potential targets for
antivirals. Drugs that target cellular
proteins required for several viral functions might not easily select for drug-resistance. They may also be active against a variety of unrelated viruses, which commonly require the same cellular
proteins, and against viral strains resistant to conventional
antiviral drugs. These
antivirals could be promptly tested against emerging viruses because even distantly related viruses commonly require the same cellular
proteins. Cellular
cyclin-dependent kinases (CDKs) are required for replication of many viruses and specific pharmacological CDK inhibitors (PCIs) are proving to have surprisingly few negative side effects in clinical trials (against
cancer). PCIs inhibit replication of wild-type and multi-
drug resistant strains of HIV, HSV-1, HSV-2, HCMV, EBV and VZV. Two PCIs,
roscovitine and
flavopiridol, were recently proven active in a mouse model of HIV-induced nephropathy. Because the
antiviral mechanisms of PCIs require no
viral proteins, mutations in viral genes may not easily overcome inhibition by these drugs. In fact, no PCI-resistant viral mutant has been reported. PCIs are scheduled to enter clinical trials as
antivirals in 2005.