Document 0778
 DOCN  M9650778
 TI    Potent inhibition of human immunodeficiency virus by MDL 101028, a novel
       sulphonic acid polymer.
 DT    9605
 AU    Taylor DL; Brennan TM; Bridges CG; Mullins MJ; Tyms AS; Jackson R;
       Cardin AD; MRC Collaborative Centre, Mill Hill, London.
 SO    Antiviral Res. 1995 Oct;28(2):159-73. Unique Identifier : AIDSLINE
       MED/96126408
 AB    MDL 101028, a novel biphenyl disulphonic acid urea co-polymer was
       designed and synthesised as a heparin mimetic. This low molecular weight
       polymer showed potent inhibition of human immunodeficiency virus type 1
       (HIV-1) replication in a number of host-cell/virus systems, including
       primary clinical isolates of the virus cultured in human peripheral
       blood mononuclear cells (PBMCs). When compared with the heterogeneous
       polysulphated molecules, heparin and dextran sulphate, this chemically
       defined compound showed equivalent antiviral activity with 50%
       inhibitory concentrations (IC50s) in the range 0.27-3.0 micrograms/ml in
       the host-cell/virus systems tested. MDL 101028 also inhibited the
       replication of HIV type 2 and the simian immunodeficiency virus (SIV),
       as well as HIV-1 variants resistant to reverse transcriptase inhibitors.
       Virus growth was blocked when exposure of T-lymphocytes to MDL 101028
       was restricted to the virus absorption stage, or even in whole blood
       conditions. MDL 101028 did not irreversibly inactivate virions, and in
       contrast to heparin, did not inhibit the attachment of radiolabelled
       HIV-1 to CD4+ T-cells. MDL 101028 blocked HIV-induced cell-to-cell
       fusion and this activity appears to explain the mechanism of its
       antiviral action. The antiviral evaluation of discrete oligomer
       molecules of MDL 101028 showed that a polymer chain length of six
       repeating units had optimal potency. The lack of anticoagulant
       properties and significant antiviral activity in whole blood may allow
       the development of MDL 101028 as a treatment of HIV infections.
 DE    Animal  Antiviral Agents/*PHARMACOLOGY  Biphenyl
       Compounds/*PHARMACOLOGY/TOXICITY  Cell Line
       Cytotoxins/PHARMACOLOGY/TOXICITY  Human  HIV-1/*DRUG EFFECTS/METABOLISM
       HIV-2/DRUG EFFECTS  Polymers/*PHARMACOLOGY  Structure-Activity
       Relationship  Sulfonic Acids/*PHARMACOLOGY  SIV/DRUG EFFECTS  JOURNAL
       ARTICLE

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