New study supports remdesivir as COVID-19 treatment

Date:
July 9, 2020
Source:
Vanderbilt University Medical Center
Summary:
A new study found that remdesivir potently inhibited SARS-CoV-2,
the virus which causes COVID-19, in human lung cell cultures and
that it improved lung function in mice infected with the virus.



FULL STORY ==========================================================================
The news about remdesivir, the investigational anti-viral drug that has
shown early promise in the fight against COVID-19, keeps getting better.


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

These preclinical findings help explain the clinical effect the drug
has had in treating COVID-19 patients. Remdesivir has been given to
patients hospitalized with COVID-19 on a compassionate use basis since
late January and through clinical trials since February.

In April, a preliminary report from the multicenter Adaptive COVID-19
Treatment Trial (which included VUMC) suggested that patients who received
the drug recovered more quickly.

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

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 UNC-Chapel Hill.



========================================================================== 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-Chapel Hill, and colleagues 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 respiratory syncytial virus, and later the Ebola virus, also showed broad
and highly potent activity against coronaviruses in laboratory tests.

The current findings, reported this week 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
is also the first to suggest that remdesivir can block the virus in a
mouse model.

Ongoing clinical trials will determine precisely how much it 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." COVID-19, which to date has infected more then
12 million people and killed nearly 600,000 worldwide, 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
efficacious 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 said.

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 the future in humans.

"We hope that will never happen, but just as we were working to
characterize 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." Others VUMC co-authors were
Amelia George, MS, Maria Agostini, PhD, Laura Stevens, MS, James Chappell,
MD, PhD, Xiaotao Lu, MS, and Tia Hughes, MS.

The 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.


========================================================================== Story Source: Materials provided by
Vanderbilt_University_Medical_Center. Original written by Bill
Snyder. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Andrea J. Pruijssers, Amelia S. George, Alexandra Scha"fer, Sarah R.

Leist, Lisa E. Gralinksi, Kenneth H. Dinnon, Boyd L. Yount, Maria L.

Agostini, Laura J. Stevens, James D. Chappell, Xiaotao Lu, Tia
M. Hughes, Kendra Gully, David R. Martinez, Ariane J. Brown, Rachel
L. Graham, Jason K. Perry, Venice Du Pont, Jared Pitts, Bin Ma,
Darius Babusis, Eisuke Murakami, Joy Y. Feng, John P. Bilello,
Danielle P. Porter, Tomas Cihlar, Ralph S. Baric, Mark R. Denison,
Timothy P. Sheahan. Remdesivir inhibits SARS-CoV-2 in human
lung cells and chimeric SARS-CoV expressing the SARS- CoV-2 RNA
polymerase in mice.. Cell Reports, 2020; 107940 DOI: 10.1016/
j.celrep.2020.107940 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200709172845.htm

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