Human lung proteins can advance or thwart SARS-CoV-2 infections: The findings could open the door to new antiviral therapies for COVID-19
Researchers have taken an important step toward understanding the microscopic battle that plays out between our lung cells and the SARS-CoV-2 virus that causes COVID-19. A UC Berkeley-led study has identified specific proteins within our bodies that can promote or protect us from SARS-CoV-2 infections, potentially opening the door to new antiviral therapies.
In the study, published this week in Nature Genetics, researchers used CRISPR technology to test the impact of every human gene on SARS-CoV-2 infections in human lung cells. Their findings revealed new pathways that the virus relies on to infect cells, as well as the antiviral pathways that help protect against viral infection. Notably, they showed that mucins — the main component of mucus found in the lungs — seem to help block the SARS-CoV-2 virus from entering our cells.
“Our data suggest that mucins play a key role in restricting SARS-CoV-2 infection by acting as a barrier to viruses that are attempting to access our lung epithelial cells,” said Scott Biering, the study’s co-lead author and a postdoctoral researcher in Eva Harris’s lab at UC Berkeley’s School of Public Health. “Further, our data suggest that mucin expression levels in an individual’s lungs may impact COVID-19 disease progression.”
Patrick Hsu — cofounder of the Arc Institute and Berkeley assistant professor of bioengineering, Deb Faculty Fellow and Innovative Genomics Institute Investigator — is the principal investigator of the study, which brought together researchers from 10 institutions. Harris, professor of public health at UC Berkeley, and Silvana Konermann, assistant professor at Stanford University School of Medicine, were co-senior authors of the study. Other collaborators contributed from Stanford University, the University of North Carolina at Chapel Hill, Yale School of Medicine and Cornell University, and spanned disciplines ranging from immunology, bioengineering, epidemiology, molecular biology and genetics.
Together, the researchers were trying to determine how the SARS-CoV-2 virus enters human cells and replicates so efficiently during illness. They also wanted to identify specific defense mechanisms in human cells that might be able to fight infection, which could inspire new therapeutic strategies.
Researchers discovered that MUC1 and MUC4, types of mucins found in lung cell membranes, defend lung cells from infection. This finding is important because previous studies had suggested that an accumulation of mucus could be the reason why some people became seriously ill with COVID-19 — since the mucus can make it difficult for people to breathe — and proposed using drugs to deplete mucus. This Berkeley-led study suggests that such a strategy could interfere with mucins that provide a valuable defense mechanism against SARS-CoV-2 infection.
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