Article Date: 20 Apr 2007
A team of German scientists has found a compound in human blood that stops HIV-1 from entering immune cells. They suggest it may lead to the development of another class of antiretroviral drugs to fight HIV/AIDS.
Their findings are published in the journal Cell.
Previous research has suggested that a number of molecules in human blood could act as inhibitors for HIV-1.
"A number of studies have suggested that some compounds in the human blood are able to inhibit HIV-1 and control it," said Prof Kirchhoff, from the University of Ulm in Germany, and co-author of the study.
In this study the researchers found a fraction of a peptide molecule called Virus-Inhibitory Peptide (VIRIP) by screening hundreds of proteins from filtered human blood.
VIRIP is part of an essential protein called alpha1-antitrypsin, the most abundant serine protease inhibitor -- proteins that stop enzymes from breaking down other proteins.
It stops HIV-1 from anchoring itself to immune cells by "interacting with the gp41 fusion peptide".
Gp41 is a part of the HIV virus that helps it to fuse with the membrane of the target immune cell, a key stage in the entry process.
Prof Kirchoff and colleagues found that by changing some of the amino acids on the VIRIP fragment they could increase its antiretroviral potency by two orders of magnitude.
They also demonstrated that VIRIP works against HIV strains that have become resistant to existing antiretrovirals.
"The findings reveal a new target for inhibiting HIV that remains fully active against viral strains that are resistant to other drugs. That's a big advantage," said Prof Kirchoff.
As HIV mutates and comes up against different drugs, it learns to develop resistance against against other drugs in the same class. So there is a need to increase the number of drug classes, each working in a different way. At present there are 20 different drug classes, say the researchers.
"You want a lot of drug classes, because multi-drug resistant viruses are starting to show up more and more. In at least some industrialized countries, it is already a severe problem," added Prof Kirchoff.
The authors concluded that:
"As a highly specific natural inhibitor of the HIV-1 gp41 fusion peptide, VIRIP may lead to the development of another class of antiretroviral drugs."
Around 40 million people live with HIV worldwide. 64 per cent of them are in Sub-Saharan Africa, by far the worst-affected region, and which according to the Joint United Nations Programme, has 12 million AIDS orphans and three quarters of all women infected with HIV.
Globally, there are between 3 and 6 million new HIV infections and 3 million deaths due to AIDS every year.
"Discovery and Optimization of a Natural HIV-1 Entry Inhibitor Targeting the gp41 Fusion Peptide."
Jan Münch, Ludger Ständker, Knut Adermann, Axel Schulz, Michael Schindler, Raghavan Chinnadurai, Stefan Pöhlmann, Chawaree Chaipan, Thorsten Biet, Thomas Peters, Bernd Meyer, Dennis Wilhelm, Hong Lu, Weiguo Jing, Shibo Jiang, Wolf-Georg Forssmann, and Frank Kirchhoff.
Cell, Vol 129, 263-275, 20 April 2007.
Written by: Catharine Paddock
Writer: Medical News Today