New Merck Antivirals in Human Tests

Merck & Co. is conducting human trials on two new antivirals,
known as L-697,639 and L-697,661. The trials began in Europe about
a month ago, and are about to begin at the U. S. National
Institutes of Health in Bethesda, Maryland. According to a Merck
spokesman quoted in the Los Angeles Times (December 22, business
section), company scientists screened 23,000 compounds to find these

two, then moved them from the laboratory to human tests in the
remarkably short time of six months. An NIH spokeswoman quoted in
the same article said that 40 asymptomatic HIV positive volunteers
were enrolled in the study at NIH.

These drugs are non-nucleoside RT inhibitors -- that is, they
block the enzyme reverse transcriptase (RT) without also being
nucleoside analogs -- false building blocks of DNA. AZT, ddC, and
ddI are RT inhibitors which are nucleoside analogs. It is hoped
that non-nucleoside drugs can be found with very little toxicity-
-since the enzyme reverse transcriptase is found only in
retroviruses and has no use in the human body, while nucleoside
analogs can in some cases affect human DNA. Other non-nucleoside RT
inhibitors are the new Boehringer Ingelheim drug BI-RG-587 discussed

in AIDS TREATMENT NEWS #117, and the class of drugs called TIBO
derivatives being developed in Europe by Janssen.

We have heard that other companies have one or more non-
nucleoside RT inhibitors in pre-clinical development, but have not
announced them. Reverse transcriptase appears to be a practical
target for anti-HIV drug development, since the enzyme is well known

and chemicals to block it can presumably be screened by laboratory
assays, without the special laboratory facilities needed for
handling live virus. It is important that more of these potential
treatments be tested, since only one drug in five which enters human

trials ever reaches marketing approval.

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