Cleveland Clinic researchers find melatonin potential COVID-19 treatment

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A new Cleveland Clinic-led study suggests that melatonin, a hormone that regulates the sleep-wake cycle and is commonly used as an over-the-counter sleep aid, may be a viable treatment option for COVID-19, according to the new results published in the journal PLOS Biology.

In the study, a novel artificial intelligence platform developed by the Lerner Research Institute to identify possible drugs for COVID-19 repurposing revealed melatonin as a promising candidate. From there, analysis of patient data from Cleveland Clinic's COVID-19 registry revealed that melatonin usage was associated with a nearly 30 percent reduced likelihood of testing positive for SARS-CoV-2, the virus that causes COVID-19, after adjusting for age, race, smoking history and various disease comorbidities. Notably, the reduced likelihood of testing positive for the virus increased from 30 to 52 percent for Black participants when adjusted for the same variables, according to the study.

The researchers harnessed network medicine methodologies and large-scale electronic health records from Cleveland Clinic patients to identify clinical manifestations and pathologies common between COVID-19 and other diseases. Specifically, they measured the proximity between host genes and proteins and those well-associated with 64 other diseases across several disease categories, such as malignant cancer and autoimmune, cardiovascular, metabolic, neurological, and pulmonary diseases,  where closer proximity indicates a higher likelihood of pathological associations between the diseases.

They found that proteins associated with respiratory distress syndrome and sepsis, two main causes of death in patients with severe COVID-19, were highly connected with multiple SARS-CoV-2 proteins. Overall, they determined that autoimmune, pulmonary, and neurological diseases showed significant network proximity to SARS-CoV-2 genes and proteins and identified 34 drugs as repurposing candidates, melatonin chief among them, the researchers said.

As COVID-19 continues to spread throughout the world, particularly with cases rising during what some have termed the "fall surge," the researchers said repurposing drugs already approved by the U.S. Food and Drug Administration for new therapeutic purposes continues to be the most efficient and cost-effective approach to treat or prevent the disease.

"Recent studies suggest that COVID-19 is a systematic disease impacting multiple cell types, tissues and organs, so knowledge of the complex interplays between the virus and other diseases is key to understanding COVID-19-related complications and identifying repurposable drugs," said Feixiong Cheng, PhD, lead author on the study and assistant staff in Cleveland Clinic's Genomic Medicine Institute, in a statement. "Our study provides a powerful, integrative network medicine strategy to predict disease manifestations associated with COVID-19 and facilitate the search for an effective treatment."

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