The new research could lead to the compound being evaluated in humans for the first time by the end of 2027.
“We have the potential to develop an antiviral that could be used to treat millions of people during large Chikungunya outbreaks, and prevent long-term disease in people who are persistently affected by this debilitating disease,” said Streblow, a professor at OHSU’s Vaccine & Gene Therapy Institute.
Streblow is leading the new research project in collaboration with Mark T. Heise, PhD, of the University of North Carolina at Chapel Hill, and Richard Whitley, MD, of the University of Alabama at Birmingham. The research team also includes scientists at the University of Colorado Denver, Southern Research in Alabama, and SRI Biosciences in California.
The Chikungunya Virus
The mosquito species whose bites spread the virus live in warmer climates. The Chikungunya virus was first identified in Africa in 1952, but it can now also be found in Asia, the Indian subcontinent, the United States, and Europe. Climate change could expand its geographic range.
Globally, more than 360,000 Chikungunya cases and 77 deaths have been identified so far this year, with most cases occurring in Brazil, India, and Guatemala. The virus began spreading in the United States in 2014; the spread was limited, and the U.S. Centers for Disease Control and Prevention reports there have been 13 locally acquired cases in U.S. states since then.
An initial bout with Chikungunya can cause fever, joint and muscle pain, a rash, and other symptoms for one to two weeks.
Young children, older adults, and those with high blood pressure or diabetes have a higher risk of experiencing severe disease or death.
While most people fully recover, about 30 to 40% will experience persistent joint pain (known as chronic Chikungunya arthritis) for months or even years. The resulting pain can be so incapacitating that some are unable to work.
Paxlovid: Anti-viral Drug for Chikungunya
Similar to the COVID drug Paxlovid, the experimental Chikungunya antiviral compound is designed to reduce the total amount of virus, or viral load.
Described as a 2-pyrimidone small molecule inhibitor, the compound patent pending works by binding to the viral RNA polymerase, through which viruses normally replicate. Streblow describes the compound as “first in class,” because it targets a unique site on viral RNA polymerase and it has never been used to treat humans before.
In previous, unpublished research involving mice, studies found the experimental antiviral reduced Chikungunya viral loads by up to 1,000 times and stopped long-term joint symptoms when it was given one to two weeks after infection.
And when the compound was given later, the research team also found that persistent viral loads, which are thought to cause long-term disease, were also reduced.
Pill to Treat Chikungunya
Now, the research team is working to tweak the antiviral compound’s chemistry and turn it into a pill that can be taken orally. The team plans to test the reformulated compound’s effectiveness and safety in more advanced animal models.
Next, the research team aims to submit an Investigational New Drug application to the U.S. Food and Drug Administration. If their application is approved, OHSU would lead a Phase 1 clinical trial to evaluate the experimental treatment’s safety and efficacy in people for the first time.
This current research is supported by the NIH’s National Institute of Allergy and Infectious Disease (contract 75N93023C00002).
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