Image showing the SARS-CoV-2 virus being attacked by a COVID-19 antiviral drug such as molnupiravir
Credit: JUAN GAERTNER/SCIENCE PHOTO LIBRARY/Getty Images

Research led by the University of Milan shows that inhibition of the lysine demethylase enzyme (LSD1) could help improve treatment of patients infected with SARS-CoV-2.

The research, published in the journal Science Signaling, shows that inhibiting LSD1 blocks the excessive and damaging inflammatory response seen in patients with COVID, but does not block the body’s natural antiviral response.

Individuals infected with SARS-CoV-2 produce type I interferons, which are drivers of antiviral immunity. While interferons are beneficial for fighting viruses, when proinflammatory cytokines are also produced by the body it can result in damage to many organs.

“Steroids, the only class of host-targeting drugs approved for the treatment of coronavirus disease 2019, indiscriminately suppress both responses, possibly impairing viral clearance,” write Pier Giuseppe Pelicci, a senior oncologist, researcher and professor at the University of Milan, and co-authors.

Finding strategies to target the cytokine response while the antiviral response remains intact could be of great benefit to patients.

In this study, Pelicci and colleagues used cell culture systems and a mouse model to investigate whether the two different immune responses seen in SARS-CoV-2 infection could be separated in mouse macrophages infected with SARS-CoV-2.

They discovered that LSD1 inhibition appeared to significantly dampen the cytokine-based proinflammatory response, while not notably impacting the normal antiviral response of the cells.

LSD1 inhibitors are already in development as high activity of this enzyme is linked to poor outcome in a number of different cancers such as bladder, lung and colorectal cancers. They are currently being tested as potential treatments for late-stage small cell lung cancer, castrate-resistant prostate cancer and acute myeloid leukemia.

“These results suggest that LSD1 controls innate immune responses against coronaviruses at multiple levels and provide a mechanistic rationale for potentially repurposing LSD1 inhibitors for COVID-19 treatment,” suggest the authors.

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