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UMBC medicinal chemist working on antiviral drugs, a possible alternative to vaccines, for the coronavirus

Katherine Seley-Radtke, a medicinal chemist and professor at the University of Maryland, Baltimore County, applied for a grant from the National Institutes of Health in 2016 to study the effectiveness of antiviral drugs against coronaviruses.

The agency denied her application, she said, citing such viruses as a minimal threat to the United States.

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So, Seley-Radtke set aside her coronavirus research and focused instead on Ebola, dengue, Zika and yellow fever. But when COVID-19 swept into the United States in March and escalated into a deadly pandemic, her phone started ringing with demand for the same ideas dismissed just four years ago.

The race to develop an answer for this infectious disease spans continents, with much of the work devoted to preventative vaccines. Treatment regimens normally require years of study, development and testing, but researchers are trying to shorten that timeline so promising therapeutics might be mass-produced by next year.

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Seley-Radtke and others say antiviral drugs could prove better at minimizing the severity of the coronavirus than vaccines — and should be prioritized.

“We’ve never been successful in developing vaccines for numerous viruses,” said Seley-Radtke, adding that even the flu vaccine does not successfully prevent thousands of cases and deaths every year. “Many of us in the antiviral field feel strongly that vaccines won’t be the answer.”

Just as patients with HIV/AIDS rely on drug “cocktails,” or a combination of medications, to treat their symptoms, COVID-19 patients will require a similar treatment approach, she said.

Already, federal officials have approved the emergency use of remdesivir, a broad-spectrum antiviral drug developed by Gilead Sciences to treat Ebola, for critically ill COVID-19 patients.

Seley-Radtke developed a compound more than two decades ago that works similarly but offers more flexibility than other antiviral drugs. Her flexible nucleoside (“fleximers”) and nucleobase (“flex-bases”) enzyme inhibitors not only stop the growth of the viruses and other diseases, but also reduce the threat of resistant strains.

Unlike remdesivir, Seley-Radtke’s compound can be administered orally, rather than via IV. It has been shown to kill SARS and MERS viruses, and most importantly, human coronaviruses, all of which have no cure and no other antiviral has successfully inhibited except for remdesivir.

“The virus develops resistance to the drug over time, so you take a drug over and over until the virus figures out you’re trying to kill it, and changes its binding site so it is no longer recognized,” she said. “Our compounds — we call them molecular chameleons — ours adapt to different environments whereas more rigid drugs can’t.”

For COVID-19, which already has evolved into several different strains, this approach could be especially useful and more effective than vaccines, which do not account for viral mutations or changes when manufactured.

Seley-Radtke said large segments of the population, such as children and people with certain allergies or health conditions, may not even be able to use vaccines. Antiviral drugs may appeal more broadly to the population, she said, and while they may not prevent infection, they might render the virus mild once administered.

Some concerns exist about antivirals’ effectiveness for critically ill patients, as the drugs generally work by preventing the virus from replicating and spreading and are typically given before a virus has progressed.

But Josh Bloom, director of chemical and pharmaceutical research at the American Council on Science and Health, said antiviral drugs may be the best bet for treating this particular disease.

“It’s just not a given that effective vaccines can be found. Sometimes, the virus wins,” he said. “An antiviral is not a cure, but it can keep people out of the hospital. That’s not saying a vaccine will be a failure, but you don’t always have a choice.”

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“We’ve never been successful in developing vaccines for numerous viruses. Many of us in the antiviral field feel strongly that vaccines won’t be the answer.”


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Bloom said successful antiviral drugs could be administered to people with COVID-19 symptoms over the course of five to 10 days like other prescriptions, hopefully turning the illness into more of a mild cold.

“For years we’ve been making antivirals for a number of diseases where vaccines aren’t available, and with luck, this will be one of them,” he said.

Bloom added that Seley-Radtke’s oral compound might be more potent than competitors, which would make it a serious contender in the pharmaceutical world. But, drug development often takes years, he said, and encouraging first phases do not necessarily mean successful outcomes.

Still, once the coronavirus commanded the spotlight on the world’s stage, Seley-Radtke sprung to action, acquiring a grant for scientists actively working on coronavirus-related projects. With the money, she could maintain the salaries of three full-time student lab workers for six months who were given special permission by UMBC to use campus facilities after the institution all but shut down in March.

The funding enabled her collaborators at UMBC and Cornell University to begin the research, successfully injecting the compound in mice at varying dosages without toxicity.

She obtained the grant from Emergent Ventures, a venture capital firm run out of George Mason University’s Mercatus Center, a free-market think tank focused on developing market-oriented ideas. In a statement, the group’s founder, Tyler Cowen, said they selected Seley-Radtke as a grant recipient because of antivirals’ potential to lower the death toll and associated health care costs from COVID-19.

Seley-Radtke said she received a grant worth $150,000 to share with three other collaborators.

She’s pursuing additional funding and has started collaborating with Maryland biotech company Healion Bio, which is developing a new class of antiviral compounds called Healions. The company is working with UMBC to license Seley-Radtke’s fleximers to develop them into therapeutics so the two drugs could form a potent drug cocktail with broad antiviral activity against all coronaviruses, as well as other deadly viruses. Such cocktails lower the chance of a virus developing resistance.

Rick Sachleben, a Boston-based retired chemist and pharmaceutical researcher, said a combination of vaccines and antivirals would be the most ideal course of action to combat the coronavirus.

“If you have an infectious disease that mutates and is constantly changing, vaccines and antivirals both become critically important — the vaccine can be used to reduce the severity of it and the antiviral provides us with treatment for when people do get infected,” he said.

Sachleben said all possibilities for preventing and treating the coronavirus should be explored, but the development of a successful and widely available vaccine may negate the purpose of an antiviral.

With so much interest in COVID-19 and a bevy of researchers throwing their hats into the ring, the fight for grant money has intensified, much to the dismay of career coronavirus researchers like Seley-Radtke.

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“We could certainly use more funding,” Seley-Radtke said. “We might not be able to get all the data because didn’t get the amount we asked for.”

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Her experience could serve as a useful lesson for those who write off certain projects or theories because of their lack of immediate relevance in the U.S. drug market, she added.

“The attitude is, ‘If it doesn’t affect us, it’s hard to get funding,‘ ” she said.

Meanwhile, at what could prove to be the apex of her career, Seley-Radtke, 62, has remained confined to her Ellicott City home. With diabetes and asthma, she could prove especially vulnerable to the very virus she’s committed to treating. She’s scarcely left the house since March, she said, leading her research team via webcam, email and text message.

It’s a departure from her usual schedule, which often takes her around the world, presenting research and appealing for funding. She’s president-elect of the International Society for Antiviral Research.

A professor at Georgia Tech, Seley-Radtke came to Washington in 2002 for an NIH peer review where she met her husband, prompting her to move her research group to UMBC. “He never funded me, just married me,” she likes to say.

Her platform has widened exponentially since the outbreak began. But the increased focus on Seley-Radtke, and on the medical field in general, has precipitated criticism of her scholarship on political rather than scientific grounds.

After publishing a piece in April about hydroxychloroquine’s ineffectiveness at treating the coronavirus — contradicting President Donald Trump’s remarks about its potential — Seley-Radtke received a slew of messages from angered supporters accusing her of endangering others. (Hydroxychloroquine has been shown to have severe side effects, especially for people with heart problems, and the Food and Drug Administration now no longer recommends prescribing it to coronavirus patients).

Despite the insults hurled her way, Seley-Radtke remains focused on her research — and on advocating for a more globalized approach to infectious diseases and treating them.

“In finding an answer to this, we’re behind,” she said. “If only they had funded me four years ago!”

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