Heme inhibits human immunodeficiency virus 1 replication in cell cultures and enhances the antiviral effect of zidovudine.
The effects of heme alone and heme administered together with 3'-azido-3'-deoxythymidine (AZT) on human immunodeficiency virus replication in human peripheral blood lymphocytes and in the H9 cell line were studied. Heme enhanced the antiviral action of AZT against both drug-resistant and drug-sensitive viral strains; the heme effect was more pronounced against the latter. Moreover, heme alone displayed a significant ability to inhibit viral replication in concentrations markedly smaller than those required to inhibit the reverse transcriptase of Rauscher murine leukemia virus. The results of this study extend the range of pharmacological actions that metalloporphyrins exert in biological systems and suggest that further study of the interactions of the natural compound heme and human immunodeficiency virus chemotherapeutic agents such as AZT may be useful.
Levere
R D
RD
Laboratory of Metabolism and Pharmacology, Rockefeller University Hospital, New York, NY 10021.
Gong
Y F
YF
Kappas
A
A
Bucher
D J
DJ
Wormser
G P
GP
Abraham
N G
NG
D000998:Antiviral Agents; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D006418:Heme / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000382:microbiology; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; D006418:Heme; D015215:Zidovudine