July 9, 2020

The news about remdesivir, the antiviral drug that showed early promise in the fight against COVID-19, keeps getting better.

This week, researchers at the University of North Carolina at Chapel Hill, Vanderbilt University Medical Center (VUMC) and Gilead Sciences reported that remdesivir greatly inhibited SARS-CoV-2, the virus that causes COVID-19, in human lung cell cultures; it also improved lung function in mice infected with the virus.

These preclinical findings explain the success the drug has had in treating COVID-19 patients. Remdesivir has been given to severely ill patients on a compassionate use basis since late January.

In April, a preliminary report from an international study suggested that patients who received the drug recovered more quickly, and Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, called the drug the new “standard of care” for coronavirus treatment.

“All of the results with remdesivir have been very encouraging, even more so than we would have hoped, but it is still investigational,” said VUMC’s Andrea Pruijssers, PhD. “It was important to directly demonstrate its activity against SARS-CoV-2 in the lab and in an animal model of disease.”

Dr. Timothy Sheahan

Dr. Timothy Sheahan

Pruijssers, research assistant professor of pediatrics at VUMC and lead antiviral scientist in the laboratory of Mark Denison, MD, is the paper’s co-corresponding author with Timothy Sheahan, PhD, assistant professor of epidemiology at the UNC Gillings School of Global Public Health.

“We performed these studies in the early days of the pandemic to demonstrate the promise of using remdesivir in humans with COVID-19,” Sheahan said. “These studies not only helped support the initial use of the drug but also played a role in the emergency approval by the FDA.”

Dr. Ralph Baric

Dr. Ralph Baric

Denison, the E.C. Stahlman Professor of Pediatrics at VUMC, directs the Division of Pediatric Infectious Diseases. He and Ralph Baric, PhD, the William R. Kenan, Jr. Distinguished Professor of epidemiology at UNC, have been studying remdesivir since 2014. They were the first to perform detailed studies to demonstrate that the drug, which was developed by Gilead Sciences to combat hepatitis C and later the Ebola virus, also showed broad and highly potent activity against coronaviruses in laboratory tests.

The current findings, reported in the journal Cell Reports, provide “the first rigorous demonstration of potent inhibition of SARS-CoV-2 in continuous and primary human lung cultures.” The study also is the first to suggest that remdesivir can block the virus in a mouse model.

Ongoing clinical trials will determine precisely how much remdesivir benefits patients in different stages of COVID-19 disease.

Meanwhile, in the laboratory, Pruijssers said: “We also are focusing on how to use remdesivir and other drugs in combinations to increase their effectiveness during COVID-19, and to be able to treat at different times of infection or by different routes, such as by mouth.”

COVID-19, which to date has infected 11 million people worldwide and killed nearly 550,000, is at least the third instance since 2003 in which a coronavirus originally transmitted from bats has caused serious illness in humans. Thus, there is an urgent need to identify and evaluate broadly effective and robust therapies that can limit and prevent coronavirus infections.

“Broad-spectrum antiviral drugs, antibodies and vaccines are needed to combat the current pandemic and those that will emerge in the future,” the researchers wrote.

In addition to SARS-CoV-2, studies in the Denison and Baric labs have shown that remdesivir is effective against a vast array of coronaviruses, including other bat viruses that could emerge in humans in the future.

“We hope that will never happen, but just as we were working to develop remdesivir over the past six years to be ready for a virus like SARS-CoV-2, we are working and investing now to prepare for any future coronavirus,” Denison said. “We want remdesivir and other drugs to be useful both now and in the future.”

“We have developed a comprehensive preclinical platform for coronavirus antiviral drug development,” added Sheahan “While we use these tools to progress drugs that address the COVID-19 pandemic, we are also anticipating COVID-30.”

Others co-authors from the UNC Gillings School are Alexandra Shäfer, Sarah R. Leist, Lisa E. Gralinski, Kenneth H. Dinnon III, Boyd L. Yount, Kendra Gully, David R. Martinez, Ariane J. Brown and Rachel L. Graham.

This study was supported by National Institutes of Health grants AI142759, AI132178 and AI132178-03S1, AI081197 and AI007151, the Dolly Parton COVID-19 Research Fund and the Elizabeth B. Lamb Center for Pediatric Research at Vanderbilt.

Contact the UNC Gillings School of Global Public Health communications team at sphcomm@unc.edu.

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