In a study on immune-compromised mice, a new treatment reduced influenza A mortality from 100% to 25% over 14 days. According to News Medical, influenza A targets the lungs to infect its victims, but researchers constructed a spherical nanoparticle coated in sialic acid that “lures the influenza A virus to its doom,” according to a News Medical report. When misted into the lungs, the nanoparticle traps influenza A and holds it until the virus self-destructs. The project is a collaboration between researchers within the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer and several institutions in South Korea including Kyungpook National University.
The new approach, which is different from existing influenza A vaccines and treatments based on neuraminidase inhibitors, could be extended to a host of viruses that use a similar approach to infecting humans such as Zika. Lead author Seok-Joon Kwon, a CBIS research scientist, coordinated the project across borders, which enabled the South Korean institutions to test a drug designed and characterized at Rensselaer, reports News Medical. A yearly influenza vaccine is effective only if it matches the strain of virus that infects the body and the virus has shown an ability to develop resistance to a class of therapeutics based on neuraminidase inhibitors.
The new solution targets an aspect of infection that does not change, specifically all hemagglutinin varieties of influenza A must bind to human sialic acid. To trap the virus, the scientists designed a dendrimer, a spherical nanoparticle with treelike branches emanating from its core, according to News Medical. The research revealed that the size of the dendrimer and the spacing between the ligands is vital to the function of the nanoparticle.
Hemagglutinin occurs in clusters of three, or “trimers,” on the surface of the virus, and researchers found that a spacing of 3 nanometers between ligands resulted in the strongest binding to the trimmers, as indicated in the News Medical report. Once bound to the densely packed dendrimer, viral neuraminidase is unable to sever the link. The coat of the virus contains millions of trimers, but the research revealed that only a few links provokes the virus to discharge its genetic cargo and ultimately self-destruct.
“Instead of blocking the virus, we mimicked its target – it’s a completely novel approach,” says Robert Linhardt, a glycoprotein expert and Rensselaer Polytechnic Institute professor who led the research. “It is effective with influenza and we have reason to believe it will function with many other viruses. This could be a therapeutic in cases where vaccine is not an option, such as exposure to an unanticipated strain, or with immune-compromised patients.”
Linhardt says, “The major accomplishment was in designing an architecture that is optimized to bind so tightly to the hemagglutinin, the neuraminidase can’t squeeze in and free the virus. It’s trapped.”
Source: News Medical