An acyclic phosphonate prodrug of HPMPC is effective against VZV in skin organ culture and mice.

ABSTRACT: Varicella zoster virus (VZV) causes chicken pox and shingles and is prevalent worldwide. Acyclovir and penciclovir (and its prodrugs) are first-line treatments for VZV infections, but they are not highly potent against VZV and resistance may arise in immunocompromised people on long-term therapy. HPMPC (cidofovir) is active against VZV, but cidofovir is not approved for treating VZV diseases, is nephrotoxic, and is not orally bioavailable. Here, we present the synthesis and evaluation of USC-373, a phosphonate prodrug of HPMPC with activity against VZV and other DNA viruses. In cultured fibroblasts, it was potent against VZV Ellen laboratory strain and was not overtly toxic, with EC₅₀ of 4 nM and CC₅₀ of 0.20 μM, producing a selectivity index of 50. In ARPE-19 cells,

SUBMITTER: Lloyd MG 

PROVIDER: S-EPMC12911940 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature