Publication
Title
CADA, a potential anti-HIV microbicide that specifically targets the cellular CD4 receptor
Author
Abstract
The cyclotriazadisulfonamide (CADA) compounds are a new class of specific CD4-targeted HIV entry inhibitors. The in vitro anti-HIV activity of CADA was shown to correlate with its ability to specifically downmodulate cell surface expression of the CD4 receptor in human cells. Here, we evaluated its potential as an anti-HIV microbicide. CADA exerted a clear CD4 receptor downregulating effect in dendritic cells (DC) and subsequently inhibited HIV-1BaL replication in DC/T cell co-cultures. The compound proved to be active against a variety of clinical isolates belonging to the HIV-1 subtypes A, B, C, D, F, G, H, AE and O. Furthermore, it prevented human T cells from being infected with the laboratory-adapted strains X4 HIV-1NL4.3 and R5 SIVmac251. Flow cytometric analysis demonstrated a significant and dose-dependent downregulation of CD4 on macaque PBMCs. In addition, the compound exerted a marked anti-SIVmac251 activity in these cells from simian origin. The combination of CADA with cellulose acetate phthalate (CAP) resulted in a synergistic inhibition of HIV-1 and SIV infection. Finally, gel formulated CADA proved to preserve the CD4 downmodulating and antiviral activity of this compound when formulated as a microbicide gel. Thus, our data suggest that CADA may have potential as a broad-spectrum anti-HIV microbicide drug candidate. The preservation of the activity of gel formulated CADA will make it now feasible for testing this unique entry inhibitor in non-human primates, not only as a single drug but also in a synergistic conjunction with other anti-HIV compounds.
Language
English
Source (journal)
Current HIV research. - Hilversum
Publication
Hilversum : 2008
ISSN
1570-162X
Volume/pages
6:3(2008), p. 246-256
ISI
000256616100008
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Publication type
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 08.10.2008
Last edited 28.06.2017
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