A team centered at the University of Minnesota has received $66 million over three years to create new antiviral drugs that could blunt the impact of the next pandemic, and perhaps yet play a role against COVID-19.
The antiviral Paxlovid has proved effective against COVID-19, but it didn't come until a year into the current pandemic. The goal of the U-led Midwest Antiviral Drug Discovery Center is to develop an "arsenal of compounds" that could be ready right away and inhibit whatever virus emerges as the next pandemic, said Reuben Harris, a co-leader of the research team.
"History says there have been pandemics and there will be more, unfortunately," he said. "History also tells us a lot about the viruses that are capable of that. We know, from all sorts of scientific efforts, that there are different virus families that are particularly capable of pandemics."
The U-led team is among nine nationwide that received $577 million in federal funding to improve pandemic preparedness. All nine will develop compounds against coronaviruses, but U researchers will be exploring therapeutics against flaviviruses, such as the mosquito-borne Zika and West Nile viruses, and against filoviruses, such as Ebola. Arenaviruses also will be targeted by the U-led research.
While viruses in those families are constantly mutating, the goal is to target their most stable components so the drugs will have better chances at working against them in the future. The research also will be modeled after the success in the world of HIV treatment —developing a combination of drugs that work together even if the virus becomes resistant to a single therapeutic.
"The end game here, too, is to have multiple drugs that target different viral essential processes and ultimately stops [the virus], which boxes it into a corner out of which it can't evolve," Harris said.
Minnesota has received nearly 40,000 courses of Paxlovid over the past six months, and used more than 13,000 to prevent people in the early stages of coronavirus infections from suffering severe COVID-19 illnesses or needing hospitalizations. The state has also received nearly 30,000 courses of a less-effective COVID-19 antiviral called molnupiravir.
Harris said there is evidence that Paxlovid could work against other coronaviruses in the future, but there also is the risk that viruses could become resistant to the lone treatment. If that happens, the U research could become important against the current pandemic as well.
"The virus will probably evolve to resist Paxlovid and other lead compounds until we reach a point where we can apply multiple drugs simultaneously," he said.
Harris also is chairman of biochemistry and structural biology at the University of Texas Health Science Center at San Antonio, which is one of 16 institutions that are part of the U-led antiviral discovery team. The other co-leader is Fang Li, a professor of structural biology of disease and director of the U's Center for Coronavirus Research. The grant effort could extend to five years and include an additional $40 million.
The funding, among other things, will accelerate existing U research with compounds and chemicals that have shown potential to inhibit viruses. The funding covers the development of compounds and initial research that they work, at which point drug companies and venture capital firms would take over and arrange clinical trials to prove whether they are safe and effective enough for federal drug approval.