ANN ARBOR – Researchers at the University of Michigan have found several FDA-approved drugs and compounds are effective in blocking or reducing SARS-CoV-2 in cells.
The study was conducted as researchers around the world scramble to discover treatments for COVID-19, according to a U-M release. While vaccines are the best defense in preventing the disease, therapies to treat it are in short supply.
For the study, researchers treated cells with 1,400 drugs and compounds, both before and after infection. Upon screening the cells, they had 17 potential hits, ten of which were newly recognized, while seven -- including remdesivir -- had already previously been identified in drug repurposing studies.
Recently published in the “Proceedings of the National Academy of Sciences,” the study used image analysis of human cell lines powered by artificial intelligence during active COVID infections.
“Traditionally, the drug development process takes a decade—and we just don’t have a decade,” assistant professor of Internal Medicine at the U-M Medical School and one of the senior authors on the paper, Jonathan Sexton, said in a release. “The therapies we discovered are well positioned for phase 2 clinical trials because their safety has already been established.”
Using various types of cells, the researchers confirmed the 17 candidate compounds. In order to mimic a COVID infection in the respiratory tract, the team tested human lung cells that were stem-cell derived. Of the 17 compounds, nine demonstrated anti-viral activity, including a protein that’s available over the counter as a dietary supplement and is also found in human breastmilk called lactoferrin.
“We found lactoferrin had remarkable efficacy for preventing infection, working better than anything else we observed,” Sexton said in a release.
He said the effectiveness of the supplement extends to variants, including the delta variant, according to early data.
Sexton’s team will soon begin clinical trials of lactoferrin to determine its ability to decrease inflammation and viral loads in COVID patients.
Sexton said there have been similar studies that identified compounds in other repurposed drugs that show potential efficacy against the virus.
“The results seem to be dependent on what cell system is used,” he said in a statement. “But there is an emerging consensus around a subset of drugs and those are the ones that have the highest priority for clinical translation. We fully expect that the majority of these won’t work in human beings, but we anticipate there are some that will.”
The study at U-M also identified a group of compounds -- traditionally used to treat cancer called MEK-inhibitors -- that seem to make COVID infections worse.
“People going in for chemotherapy are at risk already due to a lowered immune response,” Sexton said in a release. “We need to investigate whether some of these drugs worsen disease progression.”
Established in November 2019, the U-M Center for Drug Repurposing was launched by the Michigan Institute for Clinical & Health Research along with other campus partners to discover potential therapies for human diseases for which no treatments exist.
“Repurposing existing therapeutic interventions in the clinical setting has many advantages that result in significantly less time from discovery to clinical use, including documented safety profiles, reduced regulatory burden, and substantial cost savings,” co-director of MICHR and founder/executive sponsor of the Center for Drug Repurposing, George A. Mashour, said in a release.
The following researchers worked on the study with Sexton and Mashour: 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.