title: KSHV targeted therapy: an update on inhibitors of viral lytic replication.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. Since the discovery of KSHV 20 years ago, there is still no standard treatment and the management of virus-associated malignancies remains toxic and incompletely efficacious. As the majority of tumor cells are latently infected with KSHV, currently marketed antivirals that target the virus lytic cycle have shown inconsistent results in clinic. Nevertheless, lytic replication plays a major role in disease progression and virus dissemination. Case reports and retrospective studies have pointed out the benefit of antiviral therapy in the treatment and prevention of KSHV-associated diseases. As a consequence, potent and selective antivirals are needed. This review focuses on the anti-KSHV activity, mode of action and current status of antiviral drugs targeting KSHV lytic cycle. Among these drugs, different subclasses of viral DNA polymerase inhibitors and compounds that do not target the viral DNA polymerase are being discussed. We also cover molecules that target cellular kinases, as well as the potential of new drug targets and animal models for antiviral testing.
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium. natacha.coen@rega.kuleuven.be.
authors.forename: Natacha
authors.initials: N
authors.lastname: Coen
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium. sophie.duraffour@rega.kuleuven.be.
authors.forename: Sophie
authors.initials: S
authors.lastname: Duraffour
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium. robert.snoeck@rega.kuleuven.be.
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium. graciela.andrei@rega.kuleuven.be.
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006566:Herpesviridae Infections / Q000188:drug therapy*; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents