Researchers at Rensselaer Polytechnic Institute demonstrated in a paper published last month how they successfully treated immune-compromised mice exposed to the influenza virus with a new nanoparticle drug.
The drug, designed and tested by a team of RPI and South Korean researchers, uses “structural decoys” to attract the virus’ coat protein that would otherwise bind to lung cells. Once the virus adheres to the drug, it eventually “self-destructs.”
“The approach may be broadly applicable for designing effective and enduring therapeutic protection against human or avian influenza viruses,” the researchers wrote in the paper, which was published in the journal Nature Nanotechnology. In tests using the nanoparticle drug, 75 percent of immune-compromised mice survived what would have been an otherwise fatal influenza threat. Without the drug treatment, all of the mice would have died.
“We were able to demonstrate that this approach worked against live viruses,” said Robert Linhardt, a researcher and professor at RPI, who helped pinpoint the ideal carbohydrate structure to use in making the drug.
The novel nanoparticle drug method could be used to treat myriad viruses that similarly bind to particular carbohydrates in host cells. Therapies targeted at Zika virus, HIV, malaria, dengue virus and others could benefit from the team’s findings, Linhardt said.
The researchers worked across disciplines – and countries – to discover and test a nanoscale structure that, if tipped with carbohydrates targeted to bind with the flu virus, could keep the flu virus from binding with lung cells and infecting the host.
“Once bound to the influenza virus, it stays there and causes the influenza virus to become non-infective,” Linhardt said.
The live virus mice testing occurred in South Korea, while much of the preliminary research, drug development and early testing took place at RPI. Lead author Seok-Joon Kwon coordinated the international study.
“Science is not driven by one person; it’s all team-driven,” Linhardt said. “You need people with high skill sets in a lot of different areas.”
The method developed in the research would also be effective at treating against different flu virus strains because it attacks an infection process that is consistent across different strains. And the nanoparticle is designed in a way that prevents the virus from cutting itself free, as it can against some current flu treatments or other previously-tested nanoparticle structures.
The new drug could be utilized for flu strains that a vaccine cannot treat or for immune system-compromised patients.
Much remains to be learned about how the nanoparticle functions within the host’s body, and the researchers are still years from testing the drug in human trials.
“We need to figure out what happens to the drug – how is it absorbed? How is it distributed? We don’t know where it goes. How does the body clear it? How do we get rid of it?” Linhardt said, pointing to a process known as ADME studies – absorption, distribution, metabolism and excretion– which tests those questions.
The next major step for the influenza research would be to conduct another round of animal tests – this time, most likely, on ferrets, which are the “gold standard” of influenza drug-test animals, Linhardt said. The researchers are also beginning the process of constructing the nanoparticle drug anew for potential treatments of the Zika virus, which has risen to prominence in recent years due to an outbreak in South and Central America. Pregnant women infected with Zika are at particular risk, as the virus is believed to cause terrible birth defects.
The researchers are working on identifying the carbohydrate structure that would work best in attracting the binding protein of the Zika virus.
Linhardt said different viruses might best be treated with different carbohydrate and nanoparticle structures, but that the underlying principles described in the paper should hold in the treatment of other viruses that function similarly to influenza.
Reach Gazette reporter Zachary Matson at 395-3120, [email protected] or @zacharydmatson on Twitter.
An earlier version of this article listed the wrong acronym of study types. The researchers still plan to conduct ADME studies - absorption, distribution, metabolism and excretion