SELECTIVE-INHIBITION OF REPLICATION OF THE AIDS-ASSOCIATED VIRUS HTLV-III-LAV BY SYNTHETIC D-PENICILLAMINE

  • 1 January 1986
    • journal article
    • research article
    • Vol. 36-1  (2) , 184-186
Abstract
A new antimetabolite approach to block the replication of the AIDS (acquired immunodeficiency syndrome)-associated virus is described. In this communication the effect of a synthetic D-penicillamine (Trolovol) and L-penicillamine on the replication of HTLV-III/LAV was studied. The replication of HTLV-III/LAV in H9 cells was determined by measuring the expression of HTLV-III proteins p15 and p24 using monoclonal antibodies in an immunofluorescence assay system. A concentration dependent inhibition of HTLV-III replication by D- and L-penicillamine was observed. At lower concentrations L-penicillamine was more effective than D-penicillamine. However, at concentrations above 20 .mu.g/ml the inhibitory response of both isomers is similar. To obtain a total inhibition a drug concentration of 40 .mu.g/ml was needed for both isomers. Cytotoxicity of the compounds in uninfected H9 cells was observed only at high concentrations; e.g., at 500 .mu.g/ml a 32% inhibition was found for D-penicillamine and a 24% inhibition for L-penicillamine. In the presence of D- or L-penicillamine there was a significant increase in cell density of infected H9 cell cultures, indicating that both the compounds have a protective effect on H9 cells. In view of the low cytotoxicity, a selective antiviral activity against HTLV-III/LAV, and a T-cell protective effect of D-penicillamine, the evaluation of D-penicillamine for clinical treatment of AIDS is implicated.

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