`Immune Cop` Identified in Human Lungs That Detects SARS-CoV-2 Could Help Develop New COVID-19 Treatments

Scientists have identified the sensor in human lungs that detects SARS-CoV-2 and signals that it is time to mount an antiviral response, providing insights into the molecular basis of severe disease that may enable new strategies for the treatment and prevention of COVID-19.

The new study by scientists at Sanford Burnham Prebys Medical Discovery Institute (La Jolla, CA, USA) surveyed 16 viral RNA binding proteins in human lung epithelial cells and identified MDA-5 as the predominant sensor responsible for activating interferon. MDA-5 detects double-stranded viral RNA—a form that the SARS-CoV-2 virus takes when it replicates to spread the infection. Prior to this research, it was known that activating interferon is key to a coordinated immune response to the virus, but the sentinel switch that controls the process was unknown.

“Our research has shown that MDA-5 is the immune cop that’s tasked to keep an eye out for SARS-CoV-2 and call for back-up,” said Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and senior author of the study. “MDA-5 recognizes replicating viruses in lung cells and activates interferon, the body’s own frontline defender against viral invasion. Without a proper interferon response, viral infections can lead to deadly, out-of-control inflammatory reactions.”

“SARS-CoV-2 appears to disable the innate immune arm of our surveillance system, which, in the case of SARS-CoV-2 is controlled by MDA-5, and prevents the activation of interferon,” explained Chanda. “It’s the interferon response that drives the subsequent activation of many genes that exert antiviral activities—and data suggests that we need this activity to control early stages of viral infection and avoid the worst outcomes of COVID-19.”

“It’s possible that patients who become critically ill are deficient in the interferon signaling pathway,” added Chanda. “This research opens new avenues toward therapies that enhance the MDA-5 signaling to boost interferon levels early in infection to prevent severe disease. It also creates opportunities to develop COVID-19 vaccines that include an adjuvant(s) to enhance MDA-5 signaling. These would be formulations that use less ‘vaccine’ to minimize toxicity and side effects.”

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Sanford Burnham Prebys Medical Discovery Institute