Document 1110
 DOCN  M94A1110
 TI    Anti-HIV or -SIV activity of a new amphotericin-B derivative.
 DT    9412
 AU    Clayette P; Seman M; Martin M; Cherifi K; Pleskoff O; Dormont D; CEA,
       DSV/DPTE/SSA, Fontenay aux Roses, France.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):207 (abstract no. PB0843). Unique
       Identifier : AIDSLINE ICA10/94371465
 AB    OBJECTIVES. Because toxicity and antibiotic-like resistance decrease the
       antiviral activity of the present anti-HIV drugs, new molecules should
       be developped. Thereby, 1) we evaluated the anti-HIV2 or -SIVmac251
       effects of MS-8209, a less cytotoxic amphotericin derivative that
       demonstrated previously anti-HIV1 potential, and 2) we investigated its
       mode of action. MATERIAL & METHODS. 1) The antiviral activity was
       investigated toward HIV2-Rod or SIVmac251-infected HUT78 (CD4-positive
       cell line) or freshly isolated human PBMCs, according to several
       treatments (drug administration before, during or after infection). Drug
       was then maintained all along the culture. The rescue of CD4 cells was
       quantified in parallel by immunolabelling at day 7. 2) Immunomodulatory
       potential was measured by cellular thymidine incorporation with five
       activation conditions (no mitogen; PHA-P, Con A or PWM activation; PHA-P
       coupled with 10% rhIL-2). 3) The mode of action was monitored by fusion
       test (CEM expressing gp120 were cultivated with Sup T1, CPE were
       quantified at 24 hours), evaluation of antiviral activity toward
       chronically HIV1-infected cells and, DNA Hirt-PCR and DNA PCR with 24
       hrs-pre-treated PBMCs. RESULTS. MS-8209 may produce antiviral effects
       similar for HIV-1 Lai, HIV-2 Rod and SIVmac251. These anti-VIH effects
       decreased when drug was administrated after infection. In PBMC cultures,
       antiviral activity was accompanied by CD4 cell rescue, and was not
       dependent on immunosuppressor or immunostimulant effects. No inhibition
       of cell-cell fusion, and HIV replication in chronically-infected cells
       was observed. At contrary, unintegrated proviral DNA amount decreases in
       HIV-1-infected PBMCs pre-treated with MS-8209. CONCLUSION. Preliminary
       results demonstrated that MS-8209 did not inhibit gp120-CD4 binding and
       RT activity. Thereby and in regard to results described above, we may
       suggest that MS-8209 inhibit an early post-binding event. Evaluation in
       macaque model should be investigated to quantify the in vivo impact of
       this new anti-HIV drug. Likewise, considering MS-8209 mode of action,
       therapeutic combinations with dideoxynucleosides may be of interest.
 DE    Amphotericin B/*ANALOGS & DERIVATIVES/PHARMACOLOGY  Antiviral
       Agents/*PHARMACOLOGY  Cells, Cultured  Human  HIV Infections/IMMUNOLOGY
       HIV-2/*DRUG EFFECTS  Lymphocyte Transformation/DRUG EFFECTS  SIV/*DRUG
       EFFECTS  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).