Document 0740
 DOCN  M94A0740
 TI    Mechanism of action of Coumermycin A1.
 DT    9412
 AU    Jardine D; Locarnini S; Tachedjian G; Birch C; Virology Dept., Fairfield
       Hospital, Victoria.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:102 (poster no. 54).
       Unique Identifier : AIDSLINE ASHM5/94348915
 AB    AIM: To investigate the mechanism of action of Coumermycin A1 against
       HIV. METHODS: We investigated the in vitro anti HIV activity of
       coumermycin A1 in acutely infected PBLs, T-cell lines (MT-2) and
       macrophages and in chronically infected cells (H9-HTLVIIIB and
       macrophages). Several in vitro assays, such as reverse transcription and
       CD4/gp120-interaction, were used in an attempt to elucidate the specific
       mechanism of action of the drug in the acutely infected lines. In
       addition a Coumermycin resistant isolate was generated by passage of the
       virus in increasing concentrations of the drug. RESULTS: Coumermycin A1
       was active in cells acutely infected with HIV, with complete inhibition
       of the virus at 5 micrograms/ml. No inhibition of viral replication was
       observed in chronically infected cells. In vitro assays failed to locate
       the target of coumermycin in the replication cycle of HIV. Coumermycin
       resistant strains of HIV have been generated. CONCLUSION: Because
       Coumermycin inhibits HIV replication in acute but not chronic infections
       suggests that its target is at or before integration. However in vitro
       assays targeting attachment, penetration and reverse transcription have
       ruled out these processes as targets.
 DE    Antibiotics/PHARMACOLOGY  Cell Line  Coumarins/PHARMACOLOGY  Human
       HIV/*DRUG EFFECTS  In Vitro  Macrophages/MICROBIOLOGY
       T-Lymphocytes/MICROBIOLOGY  Virus Integration/DRUG EFFECTS  Virus
       Replication/*DRUG EFFECTS  MEETING ABSTRACT

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