University of Utah researchers have discovered a new class of compounds that stick to the sugary coating of the AIDS virus and inhibit it from infecting cells – an early step toward a new treatment to prevent sexual transmission of the virus.
Development and laboratory testing of the potential new microbicide to prevent human immunodeficiency virus infection is outlined in a study set for online publication by Friday in the journal Molecular Pharmaceutics.
Despite years of research, there is only one effective microbicide to prevent sexual transmission of HIV, which causes AIDS, or acquired immune deficiency syndrome. Microbicide development has focused on gels and other treatments that would be applied vaginally by women, particularly in Africa and other developing regions.
To establish infection, HIV must first enter the cells of a host organism and then take control of the cells' replication machinery to make copies of itself. Those HIV copies in turn infect other cells. These two steps of the HIV life cycle, known as viral entry and viral replication, each provide a potential target for anti-AIDS medicines.
"Most of the anti-HIV drugs in clinical trials target the machinery involved in viral replication," says the study's senior author, Patrick F. Kiser, associate professor of bioengineering and adjunct associate professor of pharmaceutics and pharmaceutical chemistry at the University of Utah.
"There is a gap in the HIV treatment pipeline for cost-effective and mass-producible viral entry inhibitors that can inactivate the virus before it has a chance to interact with target cells," he says.
Kiser conducted the study with Alamelu Mahalingham, a University of Utah graduate student in pharmaceutics and pharmaceutical chemistry; Anthony Geonnotti of Duke University Medical Center in Durham, N.C.; and Jan Balzarini of Catholic University of Leuven in Belgium.
The research was funded by the National Institutes of Health, the Bill and Melinda Gates Foundation, the Catholic University of Leuven, Belgium, and the Fund for Scientific Research, also in Belgium.
Synthetic Lectins Inhibit HIV from Entering Cells
Lectins are a group of molecules found throughout nature that interact and bind with specific sugars. HIV is coated with sugars that help to hide it from the immune system. Previous research has shown that lectins derived from plants and bacteria inhibit the entry of HIV into cells by binding to sugars found on the envelope coating the virus.
However, the cost of producing and purifying natural lectins is prohibitively high. So Kiser and his colleagues developed and evaluated the anti-HIV activity of synthetic lectins based on a compound called benzoboroxole, or BzB, which sticks to sugars found on the HIV envelope.
Kiser and his colleagues found that these BzB-based lectins were capable of binding to sugar residues on HIV, but the bond was too weak to be useful. To improve binding, they developed polymers of the synthetic lectins. The polymers are larger molecules made up of repeating subunits, which contained multiple BzB binding sites. The researchers discovered that increasing the number and density of BzB binding sites on the synthetic lectins made the substances better able to bind to the AIDS virus and thus have increased antiviral activity.
"The polymers we made are so active against HIV that dissolving about one sugar cube's weight of the benzoboroxole polymer in a bath tub of water would be enough to inhibit HIV infection in cells," says Kiser.
Depending on the strain, HIV displays significant variations in its viral envelope, so it is important to evaluate the efficacy of any potential new treatment against many different HIV strains.
Kiser and his colleagues found that their synthetic lectins not only showed similar activity across a broad spectrum of HIV strains, but also were specific to HIV and didn't affect other viruses with envelopes.
The scientists also tested the anti-HIV activity of the synthetic lectins in the presence of fructose, a sugar present in semen, which could potentially compromise the activity of lectin-based drugs because it presents an alternative binding site. However, the researchers found that the antiviral activity of the synthetic lectins was fully preserved in the presence of fructose.
"The characteristics of an ideal anti-HIV microbicide include potency, broad-spectrum activity, selective inhibition, mass producibility and biocompatibility," says Kiser. "These benzoboroxole-based synthetic lectins seem to meet all of those criteria and present an affordable and scalable potential intervention for preventing sexual transmission in regions where HIV is pandemic."
Kiser says future research will focus on evaluating the ability of synthetic lectins to prevent HIV transmission in tissues taken from the human body, with later testing in primates. Kiser and his colleagues are also developing a gel form of the polymers, which could be used as a topical treatment for preventing sexual HIV transmission.
Lee Siegel | EurekAlert!
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences