-- Recent research into the process of HIV cell fusion may lead to novel therapies for inhibiting or shutting down that process, researchers suggest in the journal Expert Opinion on Therapeutic Patents.
"Current anti-HIV therapies targeting reverse transcriptase and protease enzymes suffer from high cost, a high probability of engendering resistance, and adverse side effects following prolonged use," explained O.M.Z. Howard and colleagues at the U.S. National Cancer Institute in Maryland. "Thus, we are faced with the need to develop new antiviral strategies with more potent compounds and/or novel antiviral targets."
The success of other researchers in describing the mechanisms involved in HIV cell fusion and the proteins which mediate this process has enabled development of new targets for antiviral therapies, especially certain chemokine co-receptors, according to Howard et al. ("Inhibitors of HIV cellular fusion," Expert Opin Ther Patents, December 2000;10(12):1899-1909).
These studies have shown that HIV's fusogenic vesicle is made up of a number of different cell- and virus-derived co-receptors, all of which must act in concert to enable entry of HIV into the target cell, the researchers said.
Currently, three types of novel viral fusion inhibitors have been proposed, noted Howard and co-authors. One involves gene therapy using ribosomes to shut down the chemokine co-receptors, another uses peptide-based fusogenic antagonists to block both chemokine co-receptors and the action of the glycoprotein gp41m, while the last technique usws inhibitors of small molecules to interfere with the interaction between the virus and its co-receptors.
The researchers wrote: "HIV fusion inhibitors, like the current clinically approved agents, will need to be used in combinations consisting of antivirals that target all aspects of the HIV replication cycle and components of the fusogenic particle, to obtain optimum therapeutic effect."
The contact person for this report is O.M.Z Howard, National Cancer Institute, Molecular Immunoregulation Lab, Division of Basic Science, Frederick Cancer Research and Development Center, Building 560, Room 31 19, Frederick, MD 21702 USA.
Key points reported in this study include:
- Recent research into the process of HIV cell fusion may lead to novel therapies for inhibiting or shutting down that process
- The expense and side-effect profile of current anti-HIV strategies involving protease enzymes and/or reverse transcriptase impairs their effectiveness
- Novel fusogenic antagonists may include ribozyme-based gene therapy and/or peptide-based methods to shut down chemokine co-receptors, or small molecule inhibitors to interfere with the interaction of HIV and its co-receptors
This article was prepared by AIDS Weekly editors from staff and other reports.