HHV-8 K14 Inhibitors

The indirect inhibitors of HHV-8 K14 primarily focus on hindering viral replication and DNA synthesis, as K14 is a viral protein expressed during the replication cycle of HHV-8. These inhibitors typically target viral enzymes and processes essential for viral DNA replication and maturation. The first category includes nucleoside analogs such as Acyclovir, Ganciclovir, Valacyclovir, Famciclovir, Penciclovir, and their prodrugs. These compounds are metabolized within the infected cells to their active forms, which inhibit viral DNA polymerase. By incorporating into the growing viral DNA chain, they lead to premature termination of DNA synthesis. This action can indirectly reduce the expression of viral proteins, including HHV-8 K14, by limiting the replication of the virus.

Foscarnet and Cidofovir represent another class of antiviral agents. Foscarnet directly inhibits viral DNA polymerase without requiring activation by viral enzymes, while Cidofovir, after conversion to its active form, inhibits viral DNA synthesis. These mechanisms can lead to reduced HHV-8 K14 levels by curtailing viral replication. Letermovir and Maribavir target different aspects of the viral replication process. Letermovir inhibits the viral terminase complex, crucial for DNA packaging in the viral capsid, while Maribavir inhibits the UL97 kinase, involved in viral DNA processing and maturation. These actions can indirectly affect the expression of HHV-8 K14. Brincidofovir and Valganciclovir, prodrugs of Cidofovir and Ganciclovir respectively, are designed to improve bioavailability. They are converted into their active forms inside the body, where they exert their antiviral effects similar to their parent compounds.