Important note: Information in this article was accurate in November 2001. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, November 12, 2001
Michael Greer, Senior Medical Writer
NewsRx -- Low-molecular-weight spirodiketopiperazine derivatives can prevent cell entry by R5 strains of HIV, according to researchers in Japan and the United States.
Hiroaki Mitsuya and colleagues at the Kumamoto University School of Medicine in Kumamoto, Osaka-based Ono Pharmaceutical Co. Ltd., and the National Institutes of Health in Bethesda, Maryland, examined the antiviral efficacy of such compounds.
Some spirodiketopiperazine derivatives had highly antagonistic effects on the CCR5 coreceptor at low concentrations, Mitsuya and coworkers reported.
One compound, E913, inhibited the replication of R5 HIV strains resistant to multiple drugs at an IC50 of as low as 0.03 µM, they said. Macrophage inflammatory protein (MIP)-1(alpha), CCR5's natural ligand, was blocked from binding to its coreceptor by E913 at an IC50 of 0.002 µM.
Unfortunately, E913 had no effect on HIV strains using the CXCR4 coreceptor for cell invasion, Mitsuya and team noted. However, the compound combined synergistically with the CXCR4 antagonist AMD-3100, study data showed, and the combination was effective against R5, X4, and dual-tropic HIV strains.
E913 did not interfere with the activity of reverse transcriptase inhibitors or protease inhibitors (Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5, J Biol Chem 2001 Sep 14;276(37):35194-200.
"These data warrant that spirodiketopiperazine derivatives be further developed as potential therapeutics for HIV-1 infection," Mitsuya and coauthors concluded.
The corresponding author for this report is Hiroaki Mitsuya, Dept. of Internal Medicine II, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-0811, Japan. E-mail: hmitsuya@helix.nih.gov.
Key points reported in this study include:
This article was prepared by AIDS Weekly editors from staff and other reports.
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