Study finds existing drugs that can kill SARS-CoV2 in cells
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Since the beginning of the pandemic, researchers worldwide have been looking for ways to treat COVID-19. And while the COVID-19 vaccines represent the best measure to prevent the disease, therapies for those who do get infected remain in short supply. A new groundbreaking study from U-M reveals several drug contenders already in use for other purposes—including one dietary supplement—that have been shown to block or reduce SARS-CoV2 infection in cells.

The study, uses artificial intelligence-powered image analysis of human cell lines during infection with the novel coronavirus. The cells were treated with more than 1,400 individual FDA-approved drugs and compounds, either before or after viral infection, and screened, resulting in 17 potential hits. Ten of those hits were newly recognized, with seven identified in previous drug repurposing studies, including remdesivir, which is one of the few FDA-approved therapies for COVID-19 in hospitalized patients.

The team validated the 17 candidate compounds in several types of cells, including stem-cell derived human lung cells in an effort to mimic SARS-CoV2 infection of the respiratory tract. Nine showed anti-viral activity at reasonable doses, including lactoferrin, a protein found in human breastmilk that is also available over the counter as a dietary supplement derived from cow's milk.

"We found lactoferrin had remarkable efficacy for preventing infection, working better than anything else we observed," Sexton said. He adds that early data suggest this efficacy extends even to newer variants of SARS-CoV2, including the highly transmissible Delta variant. The team is soon launching clinical trials of the compound to examine its ability to reduce viral loads and inflammation in patients with SARS-CoV2 infection.

A surprising finding about certain drugs and COVID

Remarkably, the U-M study also identified a class of compounds called MEK-inhibitors, typically prescribed to treat cancer, that appear to worsen SARS-CoV2 infection. The finding sheds light on how the virus spreads among cells. "People going in for chemotherapy are at risk already due to a lowered immune response. We need to investigate whether some of these drugs worsen disease progression," said Sexton. The next step, he noted, is to use electronic health records to see whether patients on these drugs have worse COVID-19 outcomes.

The work is one of the first major discoveries to come out of the new U-M Center for Drug Repurposing (CDR), which was established in November 2019, just as the pandemic began. The Michigan Institute for Clinical & Health Research (MICHR), with partners across campus, launched the Center with the goal of finding potential therapeutics for the thousands of human diseases for which there is no treatment.

Source:
https://www.pnas.org/content/118/36/e2105815118
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