Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
PR Newswire, 810 Seventh Avenue, New York, NY 10019 - Wednesday, 13 November 1996.
The Nature paper describes a two-step process that allows the AIDS virus to breech the membrane of T cells. First, gp120, a protein on the surface of the AIDS virus, binds to the CD4 receptor on T cells. Once bound, the gp120- CD4 complex refolds to reveal a second structure that binds to CCR5, one of several chemokine co-receptors used by the virus to gain entry to T cells. Membrane fusion and entry of the AIDS virus into the cell follows.
Concurrent with the publication, LeukoSite announced that it will collaborate with Warner-Lambert to discover compounds that block the CCR5 receptor. The collaboration will target AIDS drugs as well as anti- inflammatory drugs that work through the CCR5 receptor.
The companies will share rights to any drugs they discover; financial terms were not disclosed. LeukoSite and Warner-Lambert have two other ongoing collaborations.
"Second structure" refines AIDS drug discovery efforts
Lead author Lijun Wu of LeukoSite said, "Our research validates the 'second structure' theory that had previously been postulated and builds on earlier work by Dr. Joseph Sodroski at Dana Farber. Now that we know a 'second structure' exists, we can study the way the gp120 CD4 complex changes shape to bind to CCR5, and use the information to improve drug discovery assays and fine tune rational drug design efforts."
The paper's authors also suggested that contagious forms of the AIDS virus may escape attack by some antibodies by keeping the 'second structure' hidden until just before it enters a target cell. "This two-step viral entry strategy may explain the failure of some treatment strategies that targeted the CD4-viral envelope complex," Wu added.
Collaboration first to target chemokine receptors
Christopher Mirabelli, Ph.D., chairman and chief executive officer of LeukoSite, said, "The LeukoSite-Warner-Lambert collaboration is the first one we know of that pairs a biotechnology company and pharmaceutical company to exploit recent discoveries in how the AIDS virus uses chemokine receptors to invade cells. We expect to move quickly because of our critical mass in chemokine research, network of academic collaborations, and ongoing relationship with Warner-Lambert."
Recently, (Science, 27 September, p. 1856) researchers at the National Cancer Institute reported that people who have two mutant copies of the gene for CCR5 are highly resistant to the AIDS virus. "We plan to develop small molecule drug antagonists to CCR5 that make the receptor invisible to the virus," Mirabelli said.
Wendell Wierenga, Ph.D., senior vice president of research at Warner- Lambert's Parke-Davis Pharmaceutical Research Division said, "The interaction of HIV with CCR5 is a promising area of research for AIDS drugs. We will integrate CCR5 discovery into Warner-Lambert's established anti-viral drug development program and pursue discovery and development as quickly as possible."
LeukoSite, Inc., a privately held biopharmaceutical company, is working on drug discovery and development strategies to treat chronic inflammatory and autoimmune diseases by blocking cellular- and tissue-specific leukocyte migration. The company has six product research and development programs underway and two drug candidates in development. In addition to Warner- Lambert, LeukoSite also has a drug discovery and development partnership with Roche Bioscience.
CONTACT: Christopher Mirabelli, Ph.D. of LeukoSite, Inc., 617-621-9350; or Douglas Johnson, Ph.D. of GreenTree Communications, 800-428-8796
Copyright (c) 1996/PR NewsWire. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Permissions Desk, PR Newswire, 810 Seventh Avenue, New York, NY 10019.
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