Research Highlights

Double shield against HIV

doi:10.1038/nindia.2011.18 Published online 10 February 2011

Researchers have designed a new class of organic compounds that can inhibit the proliferation of human immunodeficiency virus (HIV). The compounds block the activity of two specific proteins that facilitate the entry and growth of HIV in host cells.

Although highly active antiretroviral therapy (HAART) can be used to suppress HIV viral load to an undetectable level, its efficacy has been reduced by the emergence of resistant HIV strains.

To overcome the problem of drug resistance, the researchers designed potential drug molecules that aim at multiple targets. For this, the researchers synthesized caffeoyl-anilide compounds against two targets — CCR5 and integrase. The CCR5 is a receptor on human host cells that facilitates entry of the virus into host cells. Integrase is used when viral DNA is integrated into the genome of the host cell.

The anti-HIV activity of the caffeoyl-anilide compounds was carried out in CEM-GFP T cells infected with HIV-1. CEM-GFP is a type of human T cell line that expresses GFP protein upon infection with HIV. Six out of the 15 compounds showed more than 70% inhibition of HIV-1 replication in CEM-GFP cells.

The caffeoyl-anilide compounds potently inhibited the entry of CCR5-utilizing HIV virus into host cells, and also showed significant ability to inhibit integrase.

The major significance of this work is that these compounds inhibit the HIV-1 virus by two distinct mechanisms — integrase and entry inhibition. It is expected that the emerging generation of drug-resistant viruses will be significantly reduced with these new dual inhibitors, the researchers say.

The authors of this work are from: Department of Natural Products, Center for Pharmacoinformatics and Computer Center, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, and National Center for Cell Science (NCCS), Pune University Campus, Ganeshkhind, Pune, Maharashtra, India.


References

  1. Bodiwala, S. H. et al. Design and synthesis of caffeoyl-anilides as portmanteau inhibitors of HIV-1 integrase and CCR5. Bioorg. Med. Chem. 19, 1256-1263 (2011)  | Article | PubMed |