By studying the banana lectin molecule (top left) and what made it bind to both viruses and immune system cells (bottom left), the team was able to figure out how to change the way cells bind it, to make a new version (top right) that still binds viruses but doesn’t cause inflammation (bottom right). Credit: University of Michigan
The process used to create the virus-fighting form may help scientists develop even more drugs, by harnessing the “sugar code” that our cells use to communicate. That code gets hijacked by viruses and other invaders. The new research focuses on a protein called banana lectin, or BanLec, that “reads” the sugars on the outside of both viruses and cells. 5 years ago, scientists showed it could keep HIV from getting into cells – but it also caused side effects that limited its potential use.
Now they created a new form of BanLec that still fights viruses in mice, but doesn’t have a property that causes irritation and unwanted inflammation. They pinpointed the tiny part that triggered side effects. Then, they engineered a new version of BanLec, called H84T, by slightly changing the gene that acts as the instruction manual for building it. The result: a form of BanLec that worked against the viruses that cause AIDS, hepatitis C and influenza in tests in tissue and blood samples – without causing inflammation. The researchers also showed that H84T BanLec protected mice from getting infected by flu virus.
“What we’ve done is exciting because there is potential for BanLec to develop into a broad spectrum antiviral agent, something that is not clinically available to physicians and patients right now,” says David Markovitz, M.D., co-senior author of the new paper and a professor of internal medicine at the University of Michigan Medical School. “But it’s also exciting to have created it by engineering a lectin molecule for the first time, by understanding and then targeting the structure.”
The 26 international scientists used wide range of scientific tools – including X-ray techniques that let them figure out the location of every atom in the original and new forms of BanLec. Their efforts helped them understand how BanLec connects to both viruses and to sugar molecules on the outside of cells, and how it leads to irritation and other side effects by triggering signals that call in the “first responders” of the immune system.
The new version of BanLec has one less tiny spot on its surface for sugars to attach, called a “Greek key” site. This makes it impossible for sugars on the surface of immune system cells called T cells to attach in multiple spots at once and trigger inflammation. But it still allows BanLec to grab on to sugars on the surface of viruses and keep them from getting into cells. Several years of research still lie ahead before BanLec can be tested in humans.
“Tamiflu is only modestly effective, especially in critically ill patients, and influenza can develop resistance to it. But we also hope that BanLec could become useful in situations such as emergency pandemic response, and military settings, where the precise cause of an infection is unknown but a viral cause is suspected.” The team continues to test H84T BanLec against other viruses in mice and tissue samples.
Engineering a lectin molecule opens doors to other work on other lectins. Lectin molecules read the sugar code of sugar molecules that cover the surface of many viruses and cells. In fact, one of the mysteries remaining for BanLec work is just how the T cells of the immune system actually attach to it. http://medicalxpress.com/news/2015-10-drug-bananas-deadly-viruses-results.html
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