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In response to a coronavirus infection, the body's immune system mounts an inflammatory response against the virus. However, sometimes this inflammatory response is so sudden and strong that it becomes fatal.
Dr. Donald Weaver, a Senior Scientist and Director of UHN's Krembil Research Institute, recently showed in a pre-clinical study that furosemide, a small-molecule drug, has the potential to treat COVID-19 by reducing the harmful inflammation caused by the infection.
Furosemide is a diuretic commonly prescribed to treat high blood pressure, fluid build-up in the lungs and chronic kidney disease. It can be administered orally, intravenously, and by inhalation. It is also safe, readily available and part of the World Health Organization's Essential Medicines List.
It takes many years to bring a new drug to market. To accelerate the development of treatments for COVID-19, Dr. Weaver's team had turned to the strategy of repurposing existing drugs.
Searching through a library of 1,136 small molecules produced by the body, the research team found one molecule with significant anti-inflammatory potential known as 3-hydroxyanthranilic acid (3-HAA). They then looked for approved drugs that are similar in structure to 3-HAA.
Of the few candidates that were shortlisted, furosemide was the most promising. Cell culture studies revealed that furosemide inhibited the production of pro-inflammatory molecules and promoted the production anti-inflammatory molecules.
"Our pre-clinical study suggests that furosemide may be a candidate for repurposing as an inhaled therapy against COVID-19," says Dr. Weaver.
"Furosemide has been shown to reduce bronchial inflammation associated with asthma in previous clinical studies. We are currently pursuing a clinical study to assess whether it can reduce the severity of COVID-19 infection."
This work was supported by the Canada Research Chair Program and the Toronto General & Western Hospital Foundation. Dr. Weaver holds a Tier 1 Canada Research Chair in Drug Design for Protein Misfolding Disorders.