AIDSWEEKLY Plus; Monday, August 2, 2004
Staff Medical Writers

According to a study from France, "We have previously shown that styrylquinolines (SQLs) are integrase inhibitors in vitro. They compete with the long terminal repeat substrate for integrase. Here, we describe the cellular mode of action of these molecules."

"We show that SQLs do not interfere with virus entry. In fact," wrote S. Bonnenfant and colleagues, "concentrations of up to 20 times the 50% inhibitory concentration did not inhibit cell-to-cell fusion or affect the interaction between GP120 and CD4 in vitro. Moreover, the pseudotype of the retrovirus envelope did not affect drug activity."

"Quantitative reverse transcription PCR experiments showed that SQLs do not inhibit the entry of the genomic RNA. In contrast, the treatment of human immunodeficiency virus type I-infected cells with SQLs reduced the amount of the late cDNA, suggesting for the first time that integrase targeting molecules may affect the accumulation of DNA during reverse transcription," reported investigators.

Bonnenfant continued, "The cellular target of SQLs was confirmed by the appearance of mutations in the integrase gene when viruses were grown in the presence of increasing concentrations of SQLs."

"Finally, these mutations led to SQL-resistant viruses when introduced into the wild-type sequence. In contrast," the authors concluded, "SQLs were fully active against reverse transcriptase inhibitor- and diketo acid-resistant viruses, positioning SQLs as a second group of anti-integrase compounds."

Bonnenfant and colleagues published the results of their research in Journal of Virology (Styrylquinolines, integrase inhibitors acting prior to integration: a new mechanism of action for anti-integrase agents. J Virol. 2004 Jun;78(11):5728-36.

For additional information, contact H. Leh, BioalliancePharma, 59 Blvd. M Valin, F-75015 Paris, France.

The publisher of the Journal of Virology can be contacted at: American Society for Microbiology, 1752 N St. NW, Washington, DC 20036-2904 USA.

The information in this article comes under the major subject areas of HIV/AIDS, Pharmaceutical & Drug Development and Genomics & Genetics.

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

Reference

Bonnenfant S, Thomas CM, Vita C, "Styrylquinolines, integrase inhibitors acting prior to integration: a new mechanism of action for anti-integrase agents", J Virol. 2004 Jun;78(11):5728-36.

PubMED Related articles Search

040802
AW040801

Copyright © 2004 - 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, Elton John AIDS Foundation, John M. Lloyd Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2004. 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 © 1980,2004. 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.