Cosalane: New Approach to HIV Drug

Cosalane, developed by researchers at Purdue University and
the U.S. National Cancer Institute, is not yet ready for
human testing, but is interesting because it represents a new
class of drugs and new ideas for developing an HIV treatment.
The work is supported by the U.S. National Cancer Institute.

Cosalane was developed from a chemical known as ATA
(aurintricarboxylic acid), which has long been known to have
anti-HIV activity. ATA has not been developed as a drug
because it is difficult to work with. It is not a single
chemical, but a mixture of many different polymers -- and
every batch tends to be different. This creates problems for
quality control, and makes it almost impossible to get FDA
approval for marketing.

The first attempt to overcome this problem was to separate
out the smaller molecules (lower molecular weight) in the
mixture, to look for a single molecule which could be made
uniformly. But, unfortunately, the low molecular weight
molecules have the least anti-HIV activity.

Chemists then took one of these low molecular weight
components of ATA, and attached it to a steroid molecule (in
addition to making other chemical changes). The purpose was
to target the substance more effectively to the surface of
viruses and of cells. The result, cosalane, has a relatively
low molecular weight but works as well as any of the ATA
fractions.

Cosalane is believed to inhibit binding of HIV to the cell,
and also to inhibit viral entry (the fusion of the virus and
the cell, after binding). In laboratory tests, it is active
in concentrations of about 3 micromolar (not especially good
compared to other drugs), and it must be present continuously
to protect the cells. But it has been effective against all
strains of HIV-1 and HIV-2 tested, including virus which is
resistant to AZT or to the non-nucleoside RT-inhibitor drugs.
And plasma concentrations higher than the effective anti-HIV
concentration have been achieved in animal studies.

The obstacle now to cosalane's development is making enough
for further tests. Only small quantities have been
synthesized in laboratories -- not enough to finish animal
tests, let alone run a clinical trial. Efforts are now
underway to scale up the fairly complex manufacturing
process.

Little has been published about cosalane so far, although
several papers have appeared about the work with ATA which
led up to it. Mark S. Cushman, Ph.D., presented the first
technical information at a meeting of the American Chemical
Society, August 22-27, 1993. A non-technical article about
cosalane appeared in AIDS Weekly, September 6.