Blocking enzyme could hold the key to preventing, treating severe COVID-19: Infected mice lacking molecule have less inflammation, fewer blood clots in lungs

Blocking an immune response-related enzyme holds promise in preventing or treating severe COVID-19 symptoms by reducing inflammation, tissue injury and blood clots in the lungs, new research in mice suggests.

Scientists who have long studied this molecule’s functions in bacterial infections traced development of extensive lung damage in infected mice to heightened levels of the enzyme triggered by the invading SARS-CoV-2 virus.

Versions of this enzyme exist and have similar functions in both mice and humans — they’re called caspase 11 and caspase 4, respectively. After finding that the molecule is an attractive therapeutic target, researchers are exploring compounds that could safely and effectively block its activation.

“The whole idea is if this molecule is not there, the mouse will do better, which means if you target this molecule, then humans should do better,” said co-senior study author Amal Amer, professor of microbial infection and immunity in The Ohio State University College of Medicine.

The research was published online recently in Proceedings of the National Academy of Sciences.

Amer teamed with Ohio State flu and COVID virologist Jacob Yount to look into caspase 11’s role in coronavirus infection. Their labs ran a number of experiments comparing COVID infection outcomes in normal mice and mice genetically engineered so they don’t produce the enzyme.

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