The PNNL coronavirus study opens clues to combat COVID-19

Two years ago, the first case of COVID-19 appeared in the United States, right here in Washington State.

As soon as the pandemic raised its head, scientists, including from the Department of Energy Pacific Northwest National Laboratoryin Tri-Cities, focused on studying the virus that causes COVID-19 so that it can be better detected, treated and prevented.

The PNNL study on coronaviruses began long before COVID-19 became the subject of daily discussion.

In collaboration with the University of North Carolina at Chapel Hill, PNNL scientists nearly ten years ago began studying a coronavirus that causes Middle East Respiratory Syndrome or MERS.

So far MERS is not as common or contagious as COVID-19, it is more deadly and could become its own pandemic.

MERS coronavirus (MERS-CoV) is associated with severe acute coronavirus 2 respiratory syndrome (SARS-CoV 2), which causes COVID-19.

Amy Sims PNNL
Amy Sims, a virologist with PNNL, studied coronaviruses for two decades, long before the COVID-19 pandemic. Andrea Starr Pacific Northwest National Laboratory

Thus, the study of MERS-CoV one day may lead to a better treatment of many respiratory diseases, including many variants of COVID-19.

Like SARS-CoV 2, MERS-CoV attacks the lungs. As researchers deepened their understanding of how MERS-CoV damages the lungs of infected patients, they found clues that could help stop it.

Their first results are promising, including developing an approach to treating coronavirus infections using a compound that targets a cellular enzyme identified by the team.

Now scientists are looking for ways to optimize this antiviral compound and confirm its effectiveness.

The researchers began their study by investigating what causes some cells in the lungs to succumb to MERS-CoV infection.

PNNL scientists and their staff are studying the Middle East Respiratory Syndrome (MERS) coronavirus, gaining insight that could prove valuable in combating COVID-19 and other respiratory diseases. Andrea Starr Pacific Northwest National Laboratory

In the lab, they analyzed tens of thousands of measurements of specific proteins and other indicators present in lung tissue after infection.

They subsequently narrowed one of the enzymes involved in the molecular process that causes an infected cell to cause a “timeout” in response to MERS-CoV infection.

Proteins are responsible for the function and regulation of processes in our cells, tissues and organs. For a variety of reasons, including the response to infection, our bodies can begin to produce defective proteins.

When this happens, the quality control function is launched. Cellular activity shifts from the production of new proteins to emergency repairs.

If defective proteins cannot be recovered quickly enough, other proteins are sent to euthanize the cell.

The researchers found that this mechanism of transition from protein building to protein repair and ultimately cell death is very active in some MERS-CoV-infected lung cells.

This led them to identify a compound that could block the enzyme responsible for initiating this process, stopping it from occurring and preventing the resulting lung damage.

Jennifer Kyle.jpg
PNNL researchers Jennifer Kyle and Katrina Waters are studying lipids in Ebola patients. Their findings are reported in the January issue of PNAS. Andrea Starr Pacific Northwest National Laboratory

Laboratory tests at the University of North Carolina have shown that the compound stops the replication of the virus in human lung cells and improves lung function and reduces lung damage in MERS-CoV-infected mice.

MERS-CoV attacks various lung cells and settles deeper in the lungs than the virus that causes COVID-19.

Thus, while the approach to combating MERS-CoV may be inadequate to COVID-19, improving our understanding of how our bodies respond to a single coronavirus may help us find new ways to treat and prevent someone from becoming infected. killed more than 900,000 Americans.

Decades of research into the human immune system and its response to coronaviruses have provided the basis for the rapid development of vaccines against COVID-19.

These vaccines have been shown to be safe and effective in protecting against infections and reducing the risk of serious illness and death.

Additional research such as this MERS project will undoubtedly prove equally useful as we encounter new variants of COVID-19 and other coronavirus-induced diseases.

COVID-19 is not over with us yet, but when I look cautiously optimistic beyond the pandemic, it is gratifying to know that PNNL scientists and many others are pushing the boundaries of science to achieve advances in medicine that will benefit us all.

Stephen Ashby is the director of the Pacific Northwest National Laboratory in Richland.

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