Int Conf AIDS. 1992 Jul 19-24;8(3):36 (abstract no. PuA 6152). Unique
OBJECTIVE: Huminates are phenolic polymers with anionic character that
form spontaneously in soil by degradation of organic materials.
Analogous compounds with a mean Mol. Wt. of 1000 dalton were synthesized
by controlled auto-oxidation of the bi-phenoles hydrochinon and
catechin. We have evaluated the inhibition of HIV infection in cell
culture by the synthetic huminates and studied the mechanism of the
observed inhibition. METHODS: Infectivity of HIV-1LAI in MT-2 cells was
measured by counting of syncytia formed five days after infection. The
inhibitors were either present during the whole assay period, or
alternatively virus or cells were treated with inhibitors for 30 min
followed by washing prior to infection. In addition, the capacity of the
huminates to block the reverse transcriptase (RT) in HIV-lysates or the
binding of soluble CD4 to gp120 were studied. RESULTS: The catechin- and
hydrochinon-derived huminates inhibited the syncytium formation in a
dose dependent manner. Inhibitory concentrations (IC50) of 0.15
micrograms/ml and 0.5 micrograms/ml respectively were observed when the
inhibitor was present during the whole assay period. Higher
concentrations were required when virus or cells were pretreated.
However production of virus by permanently infected H9 cells was only
slightly decreased. Cytotoxic effects were observed at concentrations
higher than 20 micrograms/ml. RT is inhibited at 30 micrograms/ml, but
binding of gp120 to CD4 is not affected at this concentration.
CONCLUSIONS: Synthetic huminates are potent inhibitors of HIV infection.
Since their binding to the virus is sufficient for inhibition they most
probably interfere with an early step of infection, that is distinct
from binding of gp120 to CD4.
Antiviral Agents/*PHARMACOLOGY Catechin/*PHARMACOLOGY Cell Line Cell
Survival/DRUG EFFECTS Dose-Response Relationship, Drug Giant
Cells/DRUG EFFECTS Human Humic Acids/CHEMICAL SYNTHESIS/*PHARMACOLOGY
HIV-1/DRUG EFFECTS/*PHYSIOLOGY/PATHOGENICITY Phenols/*PHARMACOLOGY
Polymers/PHARMACOLOGY Virus Replication/*DRUG EFFECTS ABSTRACT