Brincidofovir is an oral lipid prodrug of cidofovir used in the treatment of human smallpox disease. It is a lipid conjugate pro-drug of the acyclic nucleotide analogue cidofovir. . Brincidofovir is a pro-drug comprising cidofovir conjugated to a lipid molecule - the lipid component mimics an endogenous lipid, lysophosphatidylcholine, which allows the molecule to hijack endogenous lipid uptake pathways to enter infected cells. Following uptake, the lipid molecule is cleaved to generate cidofovir, which is then phosphorylated to generate the active antiviral compound, cidofovir disphosphate. Cidofovir acts through the selective inhibition of viral DNA polymerase. After incorporation into the host cell, cidofovir is phosphorylated by pyruvate kinases to the active metabolite cidofovir diphosphate. Cidofovir diphosphate inhibits herpesvirus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerase alpha, beta, and gamma(1,2,3). Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis. Less Viral DNA is transported into the nucleus, therefore, less viral DNA is integrated into the host DNA. Less viral proteins produced, fewer viruses can form.

Brincidofovir Pathway References