Navigation path

VirApt

HIV/AIDS

Antiviral Aptamers for Treatment of HIV-1 Infection
Framework programme:
6
Call:
3
Project number:
LSHP-CT-2005-018763
EC contribution:
€ 900 000
Duration:
36 months
Type:
STREP
Starting date:
1 December 2005

Keywords: HIV; virus entry; RNA aptamers; SELEX; protein/RNA interaction; X-ray crystallography; NMR

Summary:

In this project, therapeutic RNA aptamers, which inhibit HIV entry, will be developed to give an alternative approach for the treatment of HIV infection. Aptamers are short single-stranded oligonucleotides that adopt defined, stable conformations and bind tightly to very specific targets. VirApt will primarily focus on the design of the aptamers that target membrane fusion, but will also endeavour to select aptamers that inhibit HIV entry at the level of receptor or co-receptor binding. Furthermore, the analysis of structural interaction mechanisms between RNA aptamer and virus envelope protein should provide a guide for drug design.

Background:

As the limitation of anti-HIV drug therapy becomes evident, alternative therapeutic strategies are gaining in interest. Peptides derived from the heptad repeats of the HIV-1 gp41 envelope glycoprotein have shown a strong potential to inhibit HIV-1 fusion and entry. However, the lack of bioavailability, high production costs and the rapid emergence of resistant virus strains still exclude a broad application. To overcome these disadvantages, RNA molecules interacting with the HIV-1 trimeric-coiled coil structures, and thus blocking membrane fusion, could be an option. For this purpose, VirApt combines profound expertise in oligonucleotide chemistry, analysis of RNA-protein interaction, molecular virology and the establishment of high throughput assays to study different steps of viral entry.

[+] Read More