Development of new antivirals for herpesviruses.

The long-term treatment of herpesvirus infections with current antivirals in immunocompromised hosts leads to the development of drug-resistant viruses. Because nearly all currently available antivirals finally target viral DNA polymerase, virus resistant to one drug often shows cross-resistance to other drugs. In addition, nearly all the antivirals show various kinds of side effects or poor bioavailability. This evidence highlights the need for developing new antivirals for herpesviruses that have the different viral targets. Recently, high-throughput screening of large compound collections for inhibiting specific viral enzymes, or in vitro cell culture assay, has identified several new antivirals that target different viral proteins. These include the inhibitors of helicase/primase complex, terminase complex, portal protein and UL97 protein kinase. In addition, non-nucleoside inhibitors for viral DNA polymerase have been also developed. This review will focus on these new compounds that directly inhibit viral replication.