The idea of repurposing existing medicines as a fast approach to containing COVID-19 is still popular, even as vaccines and antibodies designed to combat the disease are starting to gain steam. Scientists at the Cleveland Clinic are among those examining existing compounds as possible treatments for the coronavirus, and now they're suggesting that the popular over-the-counter sleep aid melatonin may be a possible option in treating the disease.
The researchers used an artificial intelligence tool to analyze data from 26,779 individuals in the Cleveland Clinic’s COVID-19 registry, of whom 8,274 tested positive for SARS-CoV-2, the novel coronavirus that causes COVID-19.
They found that people who were taking melatonin were 28% less likely to test positive for SARS-CoV-2, after adjusting for factors such as age, sex and underlying diseases, according to results published in the journal PLOS Biology.
The melatonin effect was more pronounced in African Americans, with a reduction of 52%. In White Americans, the number was 23%.
Melatonin is a hormone released by the body that regulates the sleep-wake cycle. As a dietary supplement, it’s commonly used to help manage insomnia and jet lag.
Besides melatonin, the Cleveland Clinic team also found that the beta-blocker carvedilol, sold under the brand Coreg for high blood pressure and other heart diseases, was associated with a 26% reduction in a person’s chance of testing positive for SARS-CoV-2.
Some members of the same Cleveland Clinic team previously pinpointed melatonin among a group of drugs they suggested might work for COVID. They showed that melatonin and mercaptopurine might work as a good combo for COVID. Those findings came from a pharmacology-based platform that used a technique called “network proximity analysis.” It was based on the idea that some proteins involved in other diseases might hold “proximity” to a virus’ interaction with the host.
The researchers applied the same method in the current study to shed a light on clinical manifestations and pathologies common between COVID-19 and 64 other diseases. Closer proximity would mean a higher likelihood of pathological associations between the diseases.
They found that proteins involved in respiratory distress syndrome and sepsis were highly connected with SARS-CoV-2. That wasn’t a surprise given that the two disorders can also cause death in patients with severe COVID-19.
“This signals to us that a drug already approved to treat these respiratory conditions may have some utility in also treating COVID-19 by acting on those shared biological targets,” Feixiong Cheng, Ph.D., the study’s senior author, said in a statement.
Overall, they identified close network proximity to SARS-CoV-2 proteins from inflammatory bowel disease, attention deficit hyperactivity disorder, as well as pulmonary diseases such as COPD. Using a computational model, they identified 34 drugs that were significantly proximal to two or more SARS-CoV-2 host protein sets.
A team at Columbia University has also linked melatonin with increased likelihood of clinical improvement among critically ill COVID-19 patients on intubation or mechanical ventilation.
The sleep-promoting supplement was also reportedly used by President Donald Trump during his COVID-19 infection, though it’s not clear if he was taking it specifically to treat the disease or as part of his daily nutrition routine.
Despite melatonin emerging as a top pick from the Cleveland Clinic registry, Cheng cautioned that larger, randomized control trials would be needed before the supplement could be widely adopted in the treatment of COVID-19.
Cheng added that AI-based approaches to analyzing COVID-19 patient registries should be embraced in the effort to find effective treatments for 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,” Cheng said. “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.”