Mushrooms cripple herpes, other viruses

Rainforests and other remote, undeveloped spots on the planet aren’t the sole source of medically useful plants. Researchers at the Medical School have discovered a mushroom that grows in their own “backyard” can cripple certain viruses.

Extract from the mushroom prevented herpes simplex virus types 1 and 2 from growing in test tubes and it reduced the severity of herpes-related eye disease in mice. It blocked influenza A, chicken pox and a respiratory virus. What’s more, the mushroom has unique characteristics that may help scientists unlock secrets about the way many viruses reproduce.

The researchers report their findings in the August issue of Antiviral Research. The active part of the mushroom, a compound they call RC-183, has been patented.

“This is a novel compound, with a structure unlike anything that’s ever been described,” says herpes expert Curtis Brandt, Medical School professor of the ophthalmology and visual sciences. “We’re hoping our studies of how it works will reveal new information about the way viruses in general replicate.”

Rozites caperata prefers to grow among the root systems of jack pine trees found thriving in places such as northern Wisconsin. It is similar in size and shape to the garden-variety cap on a stalk and like many of its relatives, cooks treasure it for its flavor. But unlike all other mushrooms, it is a powerful anti-viral substance.

Brandt says RC-183 itself may prove to be clinically effective as a topical application in treating some kinds of herpes infections in humans. But more likely, it will be developed by a pharmaceutical company as a “lead compound,” a starting point from which to fashion the most effective, least toxic herpes-hobbling drug.

“It’s also possible RC-183 may become a lead compound for a drug to treat influenza A,” says co-author on the paper Frank Piraino, an associate scientist in the department of ophthalmology and visual sciences.

Now retired from a career as a clinical virologist, Piraino first started grinding up different kinds of mushrooms he collected in parks around Milwaukee 33 years ago. When he found a free moment at work, he would mix the fungi with viruses on hand to observe the effect. He was surprised to see Rozites caperata was the only one of 26 he tested to stop a virus that causes chicken tumors. He found that it did the same thing to influenza A virus, and to herpes virus.

Piraino had his hands full directing a large laboratory that served several urban hospitals, so he filed away his mushroom project. But he resurrected it recently when retirement brought more freedom. He came to UW–Madison and showed his early findings to Brandt, who was intrigued. They’ve since worked together analyzing all aspects of the mushroom with the most sophisticated tools of molecular biology.

The Wisconsin scientists may be most excited about the lessons they hope Rozites can teach them about the inner workings of viruses. So far, they know that RC-183 contains ubiquitin, a substance that appears to play a central role in at least two cellular processes. Like a garbage/recycling truck, it removes proteins that have finished their jobs in cells. And it also helps the immune system recognize foreign antigens and mount a defense against them.

“Our challenge will be to learn exactly how RC-183 may block a ubiquitin-dependent step in virus replication,” says Brandt, also of the Department of Medical Microbiology and Immunology. “To start with, this project has shown us very clearly that concern over the disappearance of natural habitats as a source of new drugs applies universally, including to the United States, to right here in Wisconsin.”