Scientists will study how SARS-CoV-19 hijacks the immune system and creates a “cytokine storm”
Scientists at Sanford Burnham Prebys Medical Discovery Institute have received a $3 million grant from the National Institutes of Health (NIH) to study how SARS-CoV-19 weakens the immune system—and identify drugs to help infected individuals recover. The research will be led by Carl Ware, PhD, director of the Institute’s Infectious and Inflammatory Disease Center, and builds on the Institute-wide initiative to develop therapeutics to treat COVID-19.
“SARS-CoV-2 is an aggressive pathogen causing severe lung disease in unknown ways,” says Ware. “What we have learned in this short time is that severe disease is linked to an overwhelming inflammatory response—or ‘cytokine storm’—that can be potentially deadly when it leads to life-threatening pneumonia or acute respiratory distress syndrome.
“Our goal is to learn how the coronavirus inactivates the ‘good’ antiviral cytokine pathways we need to fight the virus, and instead causes too much inflammation. We will be testing drugs for their ability to reverse these harmful pathways, stop viral replication and restore our ‘healthy’ immune response.”
Cytokines
Cytokines are small, secreted proteins released by cells that regulate communications between immune cells. There are different types of cytokines; some promote inflammation, and others keep inflammation under control. A “cytokine storm” occurs when an excessive level of certain cytokines is released in response to the virus, creating high levels of inflammation in the lung—so much so that it can be fatal.
Ware’s team will be identifying SARS-CoV-19 proteins that dysregulate cytokines and screen for therapeutically active drugs to restore balance to the immune system. The team will also use animal models of coronavirus lung infection to investigate the signaling pathways that regulate antiviral cytokines. Together, the research is aimed to identify drugs that restore the body’s immune response to the virus—and understand how they work.
Ware will be working with Sumit Chanda, PhD, director of the Institute’s Immunity and Pathogenesis Program; and Evan Snyder, MD, PhD, director of the Center for Stem Cells and Regenerative Medicine at the Institute. Chanda and Snyder have also received research grants to screen for and validate existing drugs that can be repurposed to treat COVID-19.
“I’m especially pleased to be working with my colleagues, who bring expertise in drug screening, viral immunology, pharmacology and disease modeling,” says Ware. “We have a track record of success and an array of available genetic and pharmacologic tools, and we are eager to get started and help put an end to this dangerous pandemic.”