Brent Stockwell, PhD

Infection with SARS-CoV-2, the virus that causes COVID-19, causes severe pulmonary illnesses, including pneumonia and acute respiratory distress syndrome. These result in compromised lung function, sometimes resulting in death or long-term impaired lung capacity in long COVID. The reasons for this are unclear and treatment options have been limited. High levels of ferritin (a protein found in red blood cells that stores iron) in the blood and disruptions in lung iron regulation in COVID-19 patients suggest that the SARS-CoV-2 virus triggers ferroptosis, a type of cell death dependent on iron. In autopsies of lungs from fatal COVID-19 cases, we observed increased ferroptosis, not other types of cell death. In a hamster model of COVID-19, we found a clear connection between ferroptosis and lung damage. These findings indicate that ferroptosis plays a critical role in the development of COVID-19 lung disease. We will study the effect of inhibiting ferroptosis in a hamster model of COVID, which could provide new treatment options for COVID-19 patients.

Update: We have optimized the administration of two methods of ferroptosis inhibitor treatment in a COVID-19 hamster model. One is a drug-like small molecule ferroptosis inhibitor, and the other is a ferroptosis-inhibitory proprietary rodent food. We have validated the delivery of effective doses of our small molecule to the lungs, and are currently working on manufacturing our optimized rodent food. During the second year of the award, we aim to test the therapeutic potential of each of these treatments alone, and in combination, in reducing lung damage associated with SARS-CoV-2 infection in a hamster model.