COVID-19 causes ‘unexpected’ cellular response in the lungs, research finds

Scientists have discovered a surprising response to lung cells infected with the SARS-CoV-2 virus. This may explain why the treatment for this disease is so difficult. “This was completely unexpected,” says Purdue University scientist Majid Casemian, who led the study. Researchers are proposing to test new drug combinations to combat the disease. Credits: Purdue University / Rebecca McElhoe

New insights into the immune response to SARS-CoV-2 infection may provide better treatment for COVID-19 cases.

An international team of researchers found a biochemical pathway known as the immune complement system. Lung cells With the virus, it may explain why the disease is so difficult to treat.The study will be published in the journal this week Scientific immunochemistry..

Researchers suggest that a combination of antiviral drugs and drugs that block this process may be more effective.Use of in vitro model with human lungs cell, They found that the antiviral drug remdesivir, in combination with the drug ruxolitinib, inhibits this complement response.

This is despite recent evidence that trials using ruxolitinib alone to treat COVID-19 are not promising.

To identify potential drug targets, Majid Casemian, an assistant professor of computer science and biochemistry at Purdue University, said the research team had more than 1,600 previously FDA-approved drugs with known targets. I said I looked it up.

“When we looked at genes that were up-regulated by COVID-19 but down-regulated by certain drugs, ruxolitinib was the top drug with that property,” he said.

Within the past few years, scientists have found that the immune complement system, a complex system of small proteins produced by the liver that helps or complements the body’s antibodies in the fight against blood-derived pathogens, is not only intracellular. Discovered that it can function in the bloodstream.

Surprisingly, the study found that this reaction was triggered by cells in a small structure of the lung known as alveoli, Casemian said.

“We have observed that SARS-CoV2 infection of these lung cells causes the expression of activated complement systems in an unprecedented manner,” said Casemian. “This was totally unexpected for us because we didn’t think about the activation of this system inside the cell, or at least the lung cells. We usually think of the complement source as the liver. “

Claudia Kemper, Principal Investigator and Chief of the Complement and Inflammation Research Division at the National Institutes of Health, was one of the first to characterize the new role of the complement system in the immune system. She agreed that these latest discoveries were amazing.

“The complement system is traditionally thought of as a liver-derived blood circulation sentinel system that protects the host from bacterial, fungal, and viral infections,” she said. “In the context of SARS-CoV2 infection, it is unexpected that this system is rather hostile and contributes to the harmful tissue inflammation observed in severe COVID-19. This intracellular, local and complement regulation. You need to think about. Fighting COVID-19. “

Dr. Ben Afzari, a researcher at the National Institute for Diabetes, Gastroenterology and Kidney Disease, National Institute of Health, said there are signs that this will affect the difficulty of treating COVID-19. ..

“These findings are not only that complement-related genes are one of the most important pathways induced by SARS-CoV2 in infected cells, but that complement activation is inside lung epithelial cells, that is, the presence of infection. Provides important evidence of what happens locally, “he said.

“This may explain why targeting extracellular and circulating complement systems was generally disappointing with COVID-19. Cell-permeable, intracellular-acting complement gene transcription. Or the use of inhibitors of complement protein activation should be considered. “

Afzari warns that appropriate clinical trials need to be conducted to see if the combination therapy has a life-prolonging effect.

“The second finding I think is important is that the data show the potential benefits of patients with severe COVID-19 from the combination of antiviral agents with drugs that broadly target complement production or activation in infected cells. That’s a suggestion, “he said. “These data are promising, but it’s important to admit that we’ve done it. drag Treatment experiment with cell lines infected with SARS-CoV2. Therefore, by itself, it should not be used for direct treatment of patients. “

Kemper added that unexpected discoveries raise more questions.

“A currently unexplored and perhaps therapeutically interesting aspect of our observation is that the virus utilizes local complement generation and activation for its benefit, for example for the underlying processes of cell infection and replication. It’s also about whether or not to do it, “she said.

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For more information:
Bingyu Yan et al, SARS-CoV-2 promotes JAK1 / 2-dependent local complement overactivation. Scientific immunochemistry (2021). DOI: 10.1126 / sciimmunol.abg0833

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Purdue University

Quote: COVID-19 causes an “unexpected” cellular response in the lungs, according to a study (April 8, 2021) Obtained from lungs on April 8, 2021.html

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COVID-19 causes ‘unexpected’ cellular response in the lungs, research finds Source link COVID-19 causes ‘unexpected’ cellular response in the lungs, research finds

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