Targeting the cellular response to SARS-CoV-2 is promising as a new way to fight infection

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Color scanning electron micrograph of a dying (blue) cell heavily infected with SARS-CoV-2 (yellow), the virus that causes COVID-19. Credit: NIAID Integrated Research Facility, Fort Detrick, Maryland.

When a person is infected with SARS-CoV-2, the virus that causes COVID-19, it invades their cells and uses them to replicate, which puts the cells in tension. Current approaches to treating the infection target the virus itself with antiviral drugs. But Cambridge scientists have changed their approach to targeting the body’s cellular response to the virus.

In a new study, published today in the journal PLOS Pathogens, found that the three branches of a three-pointed signaling pathway called “deployed protein response” (UPR) are activated in laboratory cultures infected with SARS-CoV-2. Inhibition of UPR to restore normal cell function by drugs was also found to significantly reduce virus replication.

“The virus that causes COVID-19 activates a response in our cells (called UPR) that allows it to replicate,” said Dr. Nerea Irigoyen, of the Department of Pathology at Cambridge University, lead author of the ‘report.

He added: “Through drugs we were able to reverse the activation of this specific cellular pathway, and this significantly reduced the production of viruses inside the cells almost completely, which means that the infection could not spread to other cells. This has exciting potential as an anti-viral strategy against SARS-CoV-2. “

Treatment with a drug targeting a branch of the UPR pathway had some effect on reducing virus replication. But treatment with two drugs together (called Ceapin-A7 and KIRA8) to simultaneously target two ends of the pathway reduced virus production in cells by 99.5%. This is the first study to show that the combination of two drugs has a much greater effect on virus replication in cells than a single drug.

The approach would not prevent a person from becoming infected with the coronavirus, but scientists say the symptoms would be much milder and it would be faster.

Antiviral drugs currently used to treat COVID-19, such as remdesivir, target the replication of the virus itself. But if the virus develops resistance to these drugs, they will no longer work. Instead, the new treatment targets the response of infected cells; this will not change even if new variants appear, because the virus needs it in order to replicate.

The next step is to test the treatment on mouse models. Scientists also want to see if it works against other viruses and diseases such as and neurological disorders that also activate the UPR response in cells.

“We hope this discovery will allow the development of a broad – spectrum antiviral , effective in treating infections with other viruses as well as SARS-CoV-2. We have already discovered that it has an effect on Zika too. It has the potential to have a huge impact, “Irigoyen said.

SARS-CoV-2 is the new coronavirus responsible for the COVID-19 pandemic. Since the end of 2019 there have been more than 150 million cases of the disease worldwide and more than 3 million people have died.


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More information:
PLOS Pathogens (2021). DOI: 10.1371 / journal.ppat.1009644

Citation: Cellular response to SARS-CoV-2 is promising as a new way to fight infection (2021, June 17), retrieved June 17, 2021 at https://medicalxpress.com/news/2021- 06-cellular-response-sars-cov -infection.html

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