Polymerase substrate depletion: a novel strategy for inhibiting the replication of the human immunodeficiency virus

Mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase, shows strong anti-HIV activity in vitro in both human peripheral blood CD4+ lymphocytes and macrophages, as well as established human cell lines. MPA shows its greatest antiviral effects during the early stages of HIV infection. By limiting the rate of de novo synthesis of guanosine nucleotides, this drug apparently blocks the activity of reverse transcriptase, which is required for the formation of the HIV DNA provirus. MPA provides a novel strategy for inhibiting the replication of HIV and should be considered in clinical trials of antiviral therapies.