Anti-Inflammatory Drug (Topoisomerase 1 Inhibitor) Protects Against Lethal Inflammation from COVID-19 in Animal Models

Mount Sinai Health System researchers have found that a widely available and inexpensive drug targeting inflammatory genes has reduced morbidity and mortality in mice infected with SARS-CoV-2, the virus that causes COVID-19. In a study published online on March 30, 2021 in Cell, the team reported that the drug, topotecan (TPT), inhibited the expression of inflammatory genes in the lungs of mice as late as four days after infection, a finding with potential implications for treatment of humans. The Cell article is titled “TOP1 Inhibition Therapy Protects Against SARS-CoV-2-Induced Lethal Inflammation” ( "So far, in pre-clinical models of SARS-CoV-2, there are no therapies--either antiviral, antibody, or plasma--shown to reduce the SARS-CoV-2 disease burden when administered after more than one day post-infection" says senior author Ivan Marazzi, PhD, Associate Professor of Microbiology at the Icahn School of Medicine at Mount Sinai in New York City. "This is a huge problem because people who have severe COVID19 and get hospitalized, often do not present symptoms until many days after infection. We took a different approach, and sought to find a potential therapy that can be used during later stages of the disease. We found that the TOP1 inhibitors given days after the infection can still limit the expression of hyper-inflammatory genes in the lungs of infected animals and improve infection outcomes." Moreover, says Dr. Marazzi, topotecan (TPT), an FDA-approved topoisomerase I (TOP1) inhibitor, as well as its derivatives, are inexpensive clinical-grade inhibitors available in most countries around the world for use as antibiotic and anti-cancer agents.
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