The Next Treatment for COVID-19 Could Already Be at Your Local Pharmacy

Existing drugs kill SARS-CoV-2 in cells

Since the start of the pandemic, researchers worldwide have been looking for ways to treat COVID-19. And while the COVID-19 vaccines are the best measure to prevent the disease, therapies for those who become infected remain scarce.

A new groundbreaking study from the University of Michigan reveals several drug candidates already used for other purposes, including one dietary supplement, which has been shown to block or reduce SARS-CoV-2 infection in cells.

The study, recently published in the Proceedings of the National Academy of Sciences, uses artificial intelligence-driven 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, before or after viral infection, and screened, resulting in 17 potential hits. Ten of those hits were newly recognized, seven of which were identified in previous drug repurposing studies, including remdesivir, one of the few FDA-approved therapies for COVID-19 in hospitalized patients.

“Traditionally, the drug development process takes a decade — and we just don’t have a decade,” said Jonathan Sexton, Ph.D., assistant professor of internal medicine at UM Medical School and one of the paper’s senior authors. “The therapies we have discovered are well positioned for Phase 2 clinical trials because their safety has already been established.”

Credit: Justine Ross, Michigan Medicine

The team validated the 17 candidate compounds in several cell types, including stem cell-derived human lung cells in an attempt to mimic SARS-CoV2 respiratory infection. Nine showed antiviral activity at reasonable doses, including lactoferrin, a protein found in human breast milk and also available over the counter as a cow’s milk-based dietary supplement.

“We found that lactoferrin had remarkable efficacy for preventing infection, and that it worked better than anything else we’ve observed,” Sexton said. He adds that early data suggests this efficacy extends even to newer variants of SARS-CoV2, including the highly transmissible Delta variant.

The team will soon launch clinical trials of the compound to investigate its ability to reduce viral loads and inflammation in patients with SARS-CoV2 infection.

The trials add to the list of ongoing studies into promising reused drugs. Sexton noted that over the course of the pandemic, other drug repurposing studies have identified several compounds with potential efficacy against SARS-CoV2.

“The results seem to depend on which cell system is used,” he said.

“But there is an emerging consensus on a subset of drugs and those are the ones that have the highest priority for clinical translation. We fully expect that most of these won’t work in humans, but we expect there are some that will.” .”

Drugs and COVID: Surprising Findings

Remarkably, the UM study also identified a class of compounds called MEK inhibitors, which are commonly prescribed to treat cancer, and which appear to exacerbate SARS-CoV2 infection. The finding sheds light on how the virus spreads among cells.

“People undergoing chemotherapy are already at risk because of a lowered immune response. We need to investigate whether some of these drugs worsen disease progression,” Sexton said.

The next step, he noted, is to use electronic health records to see if patients taking these drugs have worse COVID-19 outcomes.

The work is one of the first major discoveries to come from the new UM Center for Drug Repurposing, which was established in November 2019, just as the pandemic started. The Michigan Institute for Clinical & Health Research, also known as MICHR, with partners across the campus, launched the center with the goal of finding potential therapies for the thousands of human diseases for which there is no cure.

“Reusing existing therapeutic interventions in the clinical setting has many benefits resulting in significantly reduced time from discovery to clinical use, including documented safety profiles, reduced regulatory burden, and substantial cost savings,” said George A. Mashour, MD, Ph.D. ., co-director of MICHR and founder/executive sponsor of the Center for Drug Repurposing.

Reference: “Morphological cell profiling of SARS-CoV-2 infection identifies candidate drug repurposing for COVID-19” by Carmen Mirabelli, Jesse W. Wotring, Charles J. Zhang, Sean M. McCarty, Reid Fursmidt, Carla D. Pretto, Yuanyuan Qiao, Yuping Zhang, Tristan Frum, Namrata S. Kadambi, Anya T. Amin, Teresa R. O’Meara, Jason R. Spence, Jessie Huang, Konstantinos D. Alysandratos, Darrell N. Kotton, Samuel K. Handelman, Christiane E Wobus, Kevin J. Weatherwax, George A. Mashour, Matthew J. O’Meara, Arul M. Chinnaiyan and Jonathan Z. Sexton,
DOI: 10.1073/pnas.2105815118

In addition to Sexton and Mashour, the study included the following researchers: Carmen Mirabelli, Ph.D., Jesse Wotring, Ph.D., Charles Zhang, Sean McCarty, Reid Fursmidt, Carla Pretto, Yuanyuan Qiao, Yuping Zhang, Tristan Frum, Namrata S Kadambi, Anya T. Amin, Teresa R. O’Meara, Jason R. Spence, Jessie Huang, Konstantinos D. Alysandratos, Darrell N. Kotton, Samuel K. Handelman, Christiane E. Wobus, Kevin J. Weatherwax, Matthew J O’Meara and Arul M. Chinnaiyan.