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.
Ichimura
H
H
Cancer Research Institute, University of California School of Medicine, San Francisco 94143, USA.
Levy
J A
JA
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D006150:Guanine Nucleotides / Q000378:metabolism*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000821:virology; D009173:Mycophenolic Acid / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors; D013379:Substrate Specificity; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D006150:Guanine Nucleotides; D018894:Reverse Transcriptase Inhibitors; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D009173:Mycophenolic Acid