Anti-inflammatory Therapy May Protect Against COVID-19 Inflammation

TOP1 inhibitors can limit the expression of hyper-inflammatory genes in the lungs of infected animals and improve outcomes days after the initial infection.

A recent study conducted by investigators from the Mount Sinai hospital and the Mount Sinai School of Medicine has discovered that a widely available and inexpensive therapy which targets inflammatory genes reduces morbidity and mortality in mice infected with the SARS-CoV-2 virus. Results from the study were published in the journal Cell.

The therapy, called Topotecan (TPT), inhibited the expression of inflammatory genes in the lungs of the mice as late as four days after infection.

"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" Ivan Marazzi, senior author on the study said. "This is a huge problem because people who have severe COVID19 and get hospitalized, often do not present symptoms until many days after infection.”

For the study, the investigators expanded on previous work they have done that found inhibiting the activation of inflammatory genes could help prevent animal deaths from viral and bacterial infections.

The team discovered that many anti-inflammatory therapies were not as effective as TPT because they only target a single inflammatory mediator such as IL6 or IL1.

"The fact is, a multitude of inflammatory genes and signaling pathways are dysregulated during a SARS-CoV-2 infection," Jessica Sook Yuin Ho, lead author on the study said.. "We demonstrated that TOP1 inhibitors were able to broadly or systemically dampen inflammatory gene expression in animal models, regardless of the gene or activation pathway."

The team plans for future research to evaluate the safety and efficacy of treating humans with TPT for COVID-19 at various site around the globe, including India and Singapore.

"Findings from our work suggest that repurposing the TOP1 inhibitor could be a valuable global strategy for treating severe cases of COVID-19," Marazzi said. "Particularly attractive is the fact that TPT is already FDA-approved and that its derivatives are inexpensive, with generic formulations existing throughout the world. This makes these drugs readily accessible and available for immediate use in both developing and developed countries across the world."