FLC | NIH-funded UC Davis team tests drug for COVID-19 inflammation

NIH-funded UC Davis team tests drug for COVID-19 inflammation

May 12, 2020

A drug discovered in the Bruce Hammock laboratory at the UC Davis may control the body’s inflammatory response to COVID-10 and could help patients recover, according to a nine-member research team’s commentary in the journal Cancer Metastasis and Reviews.

The drug is an inhibitor to the soluble epoxide hydrolase (sEH) enzyme, a key regulatory enzyme involved in the metabolism of fatty acids.

“COVID-19 results in excessive inflammation and a cytokine storm caused by the human body’s reaction to the SARS-CoV-2 virus,” said lead author Dipak Panigrahy, a Harvard University physician and researcher who collaborates with the Hammock laboratory. “Controlling the body’s inflammatory response to COVID-19 will likely be as important as anti-viral therapies or a vaccine. Stimulation of inflammation resolutions via pro-resolution lipid mediators that are currently in clinical trials for other inflammatory diseases is a novel approach to turning off the inflammation and preventing the cytokine storm caused by COVID-19. We propose that this drug will alleviate the cytokine storms that occur when the immune system is overwhelmed, when the patient is battling for survival.”

The work is based on more than 40 years of eicosanoid research from the Hammock lab and more than 40 years of eicosanoid research from the Charles Serhan lab at Harvard Medical School; eicosanoids are signaling molecules that play a role in regulating inflammation. Much of the research was funded by National Institutes of Health grants, including a National Institute of Environmental Health Science (River Award) to Hammock.

“We believe it holds promise to combat the inflammation involved with this disease,” said co-author Hammock. “It hit me in March that what we really need to do is not so much block cytokines as to move upstream to modulate them and resolve them rather than block inflammation.”

Hammock, a UC Davis distinguished professor who holds a joint appointment with the Department of Entomology and Nematology and the UC Davis Comprehensive Cancer Center, founded the Davis-based company EicOsis Human Health LLC, to bring the inhibitor to human clinical trials, which are underway in Texas.

Coauthor Irene Cortes-Puch, who did research at the National Institutes of Health on acute respiratory distress syndrome and sepsis, said the drug should be effective in treating acute respiratory distress syndrome in COVID-19 patients.

“We think there are a series of control systems that fail to modulate the patient’s response in COVID,” Cortés-Puch said. “The severe outcomes in some patients from the virus infection often are attributed to the cytokine storm, and blocking these cytokines represents a major therapeutic effort, which so far has failed. Our view is that we can move several steps upstream and control the cytokine storm not just at the level of individual cytokines, and in doing so, we can encourage resolution of inflammation.”