Melatonin? Stem cells? Researchers step up with unconventional approaches to COVID-19

At a time of unprecedented panic over the rapidly spreading COVID-19 coronavirus, several research groups are asking whether existing therapies could be repurposed in fighting the disease. And pretty much everything seems to be on the table, including melatonin, the hormone that’s sold over-the-counter as a sleep aid.

The melatonin suggestion was published Monday in the journal Cell Discovery by Cleveland Clinic researchers, who hit on the hormone after analyzing the genomes of 15 human coronaviruses. The team compared COVID-19 with the coronavirus that caused the SARS outbreak of 2003 using a technique called “network proximity analysis” to identify combinations of existing drugs that may be able to target cellular factors that allow the viruses to replicate.

The analysis turned up three potential drug combinations: melatonin plus chemotherapy drug mercaptopurine; sirolimus, most commonly used to prevent organ-transplant rejection, combined with another chemo drug, dactinomycin; and breast cancer drug toremifene plus emodin, a chemical found in plants like rhubarb.

The Cleveland Clinic technique is based around the idea that proteins targeted in specific diseases, like cancer, might also work as antivirals. That’s because of common protein–protein interactions and “functional pathways” that occur when viruses interact with their hosts, according to the journal article. The team used the same technique to identify potential repurposable drugs to treat Ebola a few years back.

One limitation of the Cleveland Clinic technique, the researchers warned, is that it can’t predict potential side effects of the drug combinations. Therefore, preclinical studies would need to be completed before any of the combos could be tried in people.

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Mesoblast sees a potential role for stem cells in curbing COVID-19, and now it’s suggesting repurposing its lead product candidate in treating the disease. The company announced last week that it plans to test its allogeneic mesenchymal stem cell candidate Ryoncil (remestemcel-L) in patients with acute respiratory distress caused by the virus.

The announcement came after researchers in China published a small study of Ryoncil in seven patients with pneumonia caused by COVID-19, all of whom improved after receiving the cells. Mesoblast has also completed a study of the product in 60 patients with chronic obstructive pulmonary disease, which shares some of the same inflammatory biomarkers with COVID-19, the company said. That study, which has not yet been published, showed “significantly improved pulmonary function” in patients with elevated inflammatory biomarkers, the company said in a statement.

Mesoblast has had its share of ups and downs but is now preparing for the potential FDA approval of Ryoncil in treating pediatric steroid-refractory acute graft-versus-host disease. The company is gearing up for a 2020 launch of the product in the U.S., it has told investors.