Research from UW Medicine and collaborators indicates that a drug-like molecule can activate innate immunity and induce genes to control infection in a range of RNA viruses, including West Nile, dengue, hepatitis C, influenza A, respiratory syncytial, Nipah, Lassa and Ebola.
The findings show promising evidence for creating a broad-spectrum antiviral.
“Our compound has an antiviral effect against all these viruses,” said Michael Gale Jr., University of Washington professor of immunology and director of the UW Center for Innate Immunity and Immune Disease. The finding emerged from research by his lab in concert with scientists at Kineta Inc. and the University of Texas at Galveston.
Gale said he thinks the findings are the first to show that innate immunity can be triggered therapeutically through a molecule present in all our cells, known as RIG-I.
RIG-I is a cellular protein known as a pathogen recognition receptor. These receptors detect viral RNA and signal an innate immune response inside the cell that is essential for limiting and controlling viral infections. The signal induces the expression of many innate immune and antiviral genes and the production of antiviral gene products, pro-inflammatory cytokines, chemokines and interferons.
“These products act in concert to suppress and control virus infection,” the researchers wrote.
Such activation of the innate immune response to control viral infection has been tested successfully in cells and in mice. Next steps would be to test dosing and stability in animal models and then in humans, a process that could take two to five years, Gale said.
Currently, there are no known broad-spectrum antiviral drugs and few therapeutic options against infection by RNA viruses. RNA viruses pose a significant public health problem worldwide because their high mutation rate allows them to escape the immune response. They are a frequent cause of emerging and re-emerging viral infections. West Nile virus infections, for example, started in the United States in 2000 and remerged in 2012. The World Health Organization reports 50 million to 100 million new cases of dengue fever yearly and 22,000 deaths caused by the related dengue virus. Dengue is now present in the southern U.S.
Hepatitis C, which is transmitted through the blood, infects upward of 4 million people each year; 150 million people are chronically infected and at risk for developing cirrhosis or liver cancer, according to the paper. Direct-acting antivirals can control hepatitis C and show promise of long-term cure, but viral mutation to drug resistance is a concern with prolonged use of these drugs. Also the drugs’ exorbitant costs make them unaffordable to many or most patients.
"There is tremendous interest in triggering innate immunity," said Shawn Iadonato, chief scientific officer at Seattle biotech Kineta. Some viral infections, he pointed out, cannot be treated by traditional antivirals. Activating innate immunity also will make the viruses less likely to resist the drug actions because the therapy targets the cell, via gene action, rather than the virus itself.
“It’s routine for us to think of broad-spectrum antibiotics, but the equivalent for virology doesn’t exist,” Iadonato said.