The overall objective is to develop new approaches and technologies in antiviral therapy of herpesvirus infections. Conventional antiherpesviral treatment relies solely on application of a single drug, usually blocking a viral enzyme that is essential for viral genome replication. Despite the relative success of this approach, monotherapy against a persisting pathogen has numerous disadvantages such as drug toxicity, induction of resistance and treatment failure, limited antiviral efficiency, and frequently virus recurrence after cessation of drug administration. In many clinical situations, like pregnancy, no therapeutic option exists at all due to these limitations. The development of combinatorial antiviral therapies integrating multiple drug targets has led to a complete breakthrough in the treatment of persisting viral infections like HIV/AIDS and Hepatitis B and C. Inhibitors of virus entry and fusion based on mimetic peptides to antiviral fusion glycoproteins represent a novel frontier in vital chemotherapy. Thus, for HIV, a peptide derived from the HR2 of gp41 has just been approved as a human therapeutic. Synthetic peptides derived from the HR sequences of retroviruses and paramyxoviruses have been shown to be potent inhibitors of viral fusion. Most recently, peptides derived from the HR2 of murine hepatitis CoV and SARSCoV inhibit viral entry and syncytia formation
Taking advantage of the rapidly growing knowledge of the herpesvirus gene and protein functions, combinatorial antiviral intervention strategies have now become feasible and realistic. The major objective of TargetHerpes is to define novel drug targets and to identify novel strategies for the control of herpesvirus infections. These targets and strategies will help, in the long term, to provide suitable antiviral compounds. TargetHerpes translates this knowledge into a concept of multi-pronged attack using combinatorial sets of antiviral compounds with proven antiviral efficacy in cells and a small animal model.

To this end, TargetHerpes exploits distinct steps along the herpesvirus replication cycle that allow virus inhibition. Specifically, as shown in the figure below, TargetHerpes:

1. develops peptide inhibitors that interfere with virus entry
2. generates synthetic peptides that enable antibody dependent cellular cytolysis against herpesviruses
3. defines, investigates and applies RNA silencing reagents that block the expression of viral genes that enhance herpesvirus replication
4. define, investigate and apply RNA silencing reagents that interfere with proviral host genes
5. identify viral and cellular genes involved in herpesvirus-mediated oncogenesis and define RNA silencing reagents and peptide inhibitors
   

This provides innovative technologies for the identification and development of future products targeted at preventive and therapeutic interventions for human herpesvirus diseases. Moreover, these strategies will be transferable to many other persistent infections.

Herpesvirus life cycle