gw-257406x and Epstein-Barr-Virus-Infections

To review the pharmacology, pharmacokinetics, efficacy, and safety of maribavir, a novel antiviral agent in the benzimidazole drug class.. Articles were identified through searches of MEDLINE (January 1998-July 2008). Abstracts from recent scientific meetings and the manufacturer were also included.. All English-language in vitro and in vivo studies and abstracts evaluating maribavir were reviewed and considered for inclusion. All human studies were included.. Maribavir has significant activity against both human cytomegalovirus (CMV) and Epstein-Barr virus, but not other herpesviruses. Unlike ganciclovir, which needs to be phosphorylated by UL 97 kinase to become an active inhibitor of DNA polymerase, maribavir directly inhibits UL 97 kinase. UL 97 kinase is an early viral gene product involved in viral DNA elongation, DNA packaging, and egress or shedding of capsids from viral nuclei. Maribavir has also been found to be effective against ganciclovir-resistant CMV strains. Maribavir differs from current CMV antiviral agents in its adverse event profile. Maribavir is not associated with nephrotoxicity or hematologic toxicities, but has been associated with taste disturbances. In February 2007, maribavir was granted Food and Drug Administration orphan drug status for prevention of CMV viremia and diseases in at-risk populations. Maribavir Phase 2 trials in stem-cell transplant recipients have been completed, and there are ongoing Phase 3 trials in stem-cell and organ transplant recipients.. Maribavir may be an option for treatment of ganciclovir-resistant CMV infections. Its bioavailability is greater than that of oral ganciclovir, but less than that of valganciclovir. No differences in pharmacokinetics were seen in renally impaired patients, although dialysis-dependent patients were not evaluated. Maribavir is not associated with hematologic toxicities; however, the high prevalence of taste disturbances may limit its tolerability.

Topics: Antiviral Agents; Benzimidazoles; Clinical Trials as Topic; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Viral; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Phosphotransferases (Alcohol Group Acceptor); Ribonucleosides

Topics: Antimicrobial Cationic Peptides; Antiviral Agents; Arabinofuranosyluracil; Benzimidazoles; Drug Design; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Hydroxyurea; Immunotherapy; Quinolines; Ribonucleosides; RNA, Small Interfering

Maribavir (MBV) inhibits Epstein-Barr virus (EBV) replication and the enzymatic activity of the viral protein kinase BGLF4. MBV also inhibits expression of multiple EBV transcripts during EBV lytic infection. Here we demonstrate, with the use of a BGLF4 knockout virus, that effects of MBV on transcription take place primarily through inhibition of BGLF4. MBV inhibits viral genome copy numbers and infectivity to levels similar to and exceeding levels produced by BGLF4 knockout virus.

Topics: Antiviral Agents; Benzimidazoles; Cell Line; Down-Regulation; Epstein-Barr Virus Infections; Gene Expression Regulation, Viral; Genome, Viral; Herpesvirus 4, Human; Humans; Protein Serine-Threonine Kinases; Ribonucleosides; Viral Proteins; Virus Replication