Antiviral Intervention, Resistance and Perspectives
Detlef Michel and Thomas Mertens
from: Cytomegaloviruses: Molecular Biology and Immunology (Edited by: Matthias J. Reddehase). Caister Academic Press, U.K. (2006)
Abstract
Four drugs, ganciclovir/valganciclovir, cidofovir, foscarnet and fomivirsen, have been approved for the treatment of HCMV diseases. Partially they have also been used for prophylaxis or preemptive therapy of active infections. Some studies have shown a limited prophylactic effect of aciclovir (ACV) after organ transplantation, but conflicting results do exist. The first-line therapeutic nucleoside analogue ganciclovir (GCV) but also ACV is activated by the viral UL97 protein (pUL97). Except for fomivirsen, all of these drugs share the same target molecule, the viral DNA polymerase. The compounds provoke significant drug-specific side effects and the emergence of clinically relevant drug-resistant HCMV has been reported for all of them. Therefore, new compounds are urgently needed with less adverse effects, good oral bioavailability and possibly novel mechanisms of action to avoid cross-resistance. Consequently, new drugs and mechanisms of action as well as new molecular targets have to be identified. Benzimidazoles, phenylenediaminesulphonamides, and indolocarbazole protein kinase inhibitors are promising lead compounds for the development of even more specific inhibitors of HCMV. Inhibition of virus entry might be an imminent target for future antivirals. Since many symptoms of HCMV disease are quite unspecific, virologists have to provide reliable and fast methods for quantitative diagnosis of active systemic viral infection. Furthermore, for an optimum management of patients, monitoring of successful therapy, as well as early detection of drug resistant HCMV emerging under therapy have to be performed read more ...
