Non-Nucleoside Inhibitors of the Human Cytomegalovirus

The human cytomegalovirus (HCMV) is a highly prevalent member of the herpesvirus family responsible for opportunistic infections in immunocompromised individuals such as organ transplant recipients, AIDS patients and newborn infants. The advent of HAART as an effective control for AIDS has reduced the demand for anti-HCMV drugs in AIDS patients, but HCMV remains a significant challenge in organ transplant therapy. As resistance to HAART emerges, HCMV has the potential to become a significant risk for those infected with HIV. Existing chemotherapies for the treatment of HCMV infections suffer from toxicity, poor bioavailability and tolerability. These drugs also do not clear the virus.A number of strategies have been employed to find new therapeutic agents. Non-nucleoside inhibitors of HCMV are reviewed in the present paper. These compounds inhibit viral growth by interfering with viral molecular functions and also by intercepting host cell processes. General classes of potential drugs discussed include HCMV protease inhibitors, compounds preventing viral DNA replication and materials with unknown mechanisms of action. Natural products, rationally resigned inhibitors and compounds found by high throughput methods are described.