Introduction

Most of herpesviruses are responsible for serious infections also in humans. First-line choice for treatment of herpes infections are nucleoside analogues (e.g., ganciclovir) which unfortunately may cause serious side effects. The objective of this invention is the identification of a new antiviral drug for the treatment of Herpesvirus infection, including Congenital Human cytomegalovirus (HCMV) congenital infections.

Technical features

Herpesviruses are double stranded DNA viruses with icosaedric symmetry belonging to the family Herpesviridae. Most of herpesviruses are responsible for serious infections also in humans. First-line choice for treatment of herpes infections are nucleoside analogues (e.g., ganciclovir) which unfortunately may cause considerable toxicity to the host. In addition, treatment of congenitally infected newborns or transplanted recipients with ganciclovir or similar nucleoside causes serious side effects due to high myelotoxicity that limits their employment significantly. Nucleoside analogues are also known to induce resistance mutations on genes coding for viral enzymes involved in DNA synthesis (e.g. UL54 or UL97 of HCMV). To this end, the identification of a cellular protein of the host as target to block viral replication would allow to tackle the occurrence of genome mutations. The objective of this invention is the identification of a host cell protein involved in the replication of a virus of the Herpesviridae family. The objective is achieved by targeting PAD2 (peptidyl arginine deiminase type 2) and providing inhibitors, antagonists and related compositions to be employed as antiviral agents against viruses of the Herpesviridae family.

Possible Applications

• Prevention and protection of CMV disease for:
  • Transplant recipients;
  • Pregnants;
  • “Pre‐emptive therapy” of organ recipients.

Advantages

• Higher specificity;
• Lower cytotoxicity;
• New target: overcome antiviral drug resistance displayed by currently available compounds.