Inside the Vanderbilt lab researching a promising new COVID-19 treatment

NASHVILLE — The quiet hum of equipment underscored the lab as Dr. Mark Denison and his colleagues got to work at Vanderbilt University Medical Center on an early October morning.

Denison wove between benches full of pipettes, centrifuges and microscopes while he talked about their research into a promising antiviral drug that could dramatically reduce severe cases of COVID-19 and prevent hospitalizations.

Molnupiravir, made by Merck & Co. and Ridgeback Biotherapeutics of Miami, prevented half of severe coronavirus infections that would otherwise have sent people to the hospital, according to a study released earlier this month. The companies are in discussions with the FDA and plan to apply for emergency use authorization as quickly as possible.

Study: New antiviral is highly effective and is stirring hope that COVID-19 could be treated by a pill

Britain announced its approval of molnupiravir on Nov. 4, becoming the first nation to approve a pill to treat COVID-19. British Health Secretary Sajid Javid called it a historic day for the nation, heralding the "ground-breaking" treatment. 

Denison and his team, along with colleagues at the University of North Carolina at Chapel Hill and Emory University, led the development of molnupiravir starting in 2016.

"We had the specific purpose of preparing for a pandemic and treating diseases like MERS," he said. 

They were the first to show how well molnupiravir worked to fight COVID-19. They also showed that it kept the coronavirus from becoming resistant to the drug itself. 

So far, antiviral drug remdesivir is the only COVID-19 treatment with full FDA approval. Eleven more are permitted under the Emergency Use Authorization, including monoclonal antibodies, according to the FDA.

But unlike remdesivir and monoclonal antibodies, which are given by IV and often not used until someone is severely ill, molnupiravir can be taken by mouth as a pill when symptoms first surface — or even sooner.

That's a game-changer, said Denison, who is also the director for VUMC's division of pediatric infectious diseases.

It could curb the virus early in an infection, before it gets worse. It could also be given after COVID-19 exposure to those who are at high risk of severe disease or death, including the immunocompromised, immunosuppressed and elderly, and those unable to get vaccinated.

Denison likened it to Tamiflu, an antiviral commonly used against influenza. Tamiflu has been shown to shorten the course of the flu and can be used to prevent infection in someone who is exposed to it. 

Even with strides in the development of antiviral drugs for COVID-19, Denison said his goal is much larger. 

"I've always tried to work myself out of a job, where we can find mechanisms for aborting coronavirus infections," he said. "I would be thrilled if we never needed an antiviral, if everybody got vaccinated." 

Billions of dollars, years of research bolster emerging COVID-19 treatments

Public health officials and researchers have worked relentlessly to find antivirals that treat COVID-19 since early in the pandemic. Hundreds of drugs are currently in development or undergoing trials, according to the FDA. 

But years before antivirals like molnupiravir and remdesivir were in the spotlight, Denison and his team at Vanderbilt were researching them, along with different kinds of coronaviruses. 

"This stuff doesn't come fully formed from the head of Zeus," Denison said. "It takes a lot of time, a lot of work."

Denison describes himself as an infectious disease specialist and virologist who has been studying coronaviruses since 1984.

He started out with a short-term project on how coronaviruses replicate inside a cell.

"My six-week project has turned into 36 years," he quipped.

Denison nearly gave up on his work with coronaviruses in 2003, after spending years fighting for grants to fund his research. The emergence of SARS in the early 2000s, followed by MERS a decade later — respiratory diseases both caused by a coronavirus — reignited his work. 

Now, even that chapter of Denison's career is in stark contrast to his current work.

In June, President Joe Biden's administration allocated $3.2 billion toward the development of antivirals, saying the drugs would be a crucial part of the battle against COVID-19. Roughly a third of that was earmarked to buy 1.7 million doses of molnupiravir if the drug met the FDA's safety and effectiveness standards. 

Denison smiled as he added that country music icon and Tennessee native Dolly Parton also helped fund his team's research. Her $1 million contribution aided the development  of COVID-19 treatments at Vanderbilt, along with the Moderna COVID-19 vaccine. Parton cited as inspiration her longtime friendship with Dr. Naji Abumrad, a Vanderbilt doctor who has been involved with research there for years. 

There's still more work ahead for Denison and his nine-person team as they continue to study and develop molnupiravir. And while the development of effective antiviral treatments for COVID-19 is remarkable, Denison emphasized the importance of vaccination. 

"If I have a message about antivirals, it's that we shouldn't depend on them," he said. "They shouldn't be a substitute for vaccination." 

Find reporter Rachel Wegner on Twitter @rachelannwegner.