AIDSWEEKLY Plus; Monday, June 2, 2003
Staff Medical Writers

"During the assembly stage of the human immunodeficiency virus (HIV) replication cycle, several thousand copies of the viral Gag polyprotein associate at the cell membrane and bud to form an immature, non-infectious virion," scientists at the University of Maryland explained. "Gag is subsequently cleaved by the protease, which liberates the capsid proteins for assembly into the polyprotein shell of the central core particle (or capsid) of the mature virus."

"Viral infectivity is critically dependent on capsid formation and stability, making the capsid protein a potentially attractive antiviral target," according to C. Tang and coauthors, who "identified compounds that bind to an apical site on the N-terminal domain of the HIV-1 capsid protein and inhibit capsid assembly in vitro."

"One compound, N-(3-chloro-4-methylphenyl)-NN'{2-[({5-[(dimethylamino)-methyl]-2-furyl}-methyl)-sulfanyl]ethyl}urea) (CAP-1), is well tolerated in cell cultures, enabling antiviral and mechanistic studies," they reported. "CAP-1 inhibits HIV-1 infectivity in a dose-dependent manner, but does not interfere with viral entry, rev transcription, integration, proteolytic processing, or virus production, indicating a novel antiviral mechanism."

"Significantly, virus particles generated in the presence of CAP-1 exhibit heterogeneous sizes and abnormal core morphologies, consistent with inhibited CA-CA interactions during virus assembly and maturation," study results revealed.

"These findings lay the groundwork for the development of assembly inhibitors as a new class of therapeutic agents for the treatment of AIDS," the researchers concluded.

Tang and colleagues published their study in the Journal of Molecular Biology (Antiviral inhibition of the HIV-1 capsid protein. J Mol Biol 2003 Apr 11;327(5):1013-20.

Additional information can be obtained by contacting M.F. Summers, University of Maryland, Howard Hughes Medical Institute, 1000 Hilltop Circle, Baltimore, MD 21250, USA.

The publisher of the Journal of Molecular Biology can be contacted at: Academic Press Ltd. Elsevier Science Ltd., 24-28 Oval Rd., London NW1 7DX, UK.

The information in this article comes under the major subject areas of AIDS and HIV, Drug Development and Proteomics.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Tang C, Loeliger E, Kinde I, et al., "Antiviral inhibition of the HIV-1 capsid protein", J Mol Biol 2003 Apr 11;327(5):1013-20.

PubMED Related articles Search

030602
AW030603

Copyright © 2003 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA. Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588 http://www.newsrx.net

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2003. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright © 1980,2003. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content.