Study reveals existing drugs that kill SARS-CoV2 in cells

The study, published recently in the Proceedings of the National Academy of Sciences, uses artificial intelligence-powered image analysis of human cell lines during infection with the novel coronavirus. The cells were treated with over 1,400 drugs and individual compounds approved by the FDA, before or after viral infection, and screened, yielding 17 potential results. Ten of those successes have been newly recognized, seven of which were identified in previous drug reassignment studies, including remdesivir, which is one of the few FDA-approved treatments for COVID-17 in hospital patients.

“Traditionally, the process of developing a drug 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 the ‘one of the main authors on the paper. “The therapies we have discovered are well positioned for Phase 2 clinical trials because their safety has already been established.”

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

“We found that lactoferrin was remarkably effective in preventing infection, working better than anything we’ve seen,” Sexton said. He adds that early data suggests that 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 examine its ability to reduce viral loads and inflammation in patients infected with SARS-CoV2.

The trials add to the list of ongoing studies of promising reused drugs. Sexton noted that during the pandemic, other drug reorientation studies identified different compounds potentially effective against SARS-CoV2. “The results appear to depend on the cellular system used,” he said.

“But there is an emerging consensus around a subset of drugs and these are the ones that have the highest priority for clinical translation. We fully expect that the majority of them will not work in patients. human beings, but we expect some. “

A surprising discovery on certain drugs and COVID

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

“People who take chemotherapy are already at risk due to a reduced immune response. We need to determine whether any of these drugs are making disease progression worse,” 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 findings to emerge from the new UM Center for Drug Reuse (CDR), which was established in November 2019, just at the start of the pandemic. The Michigan Institute for Clinical & Health Research (MICHR), along with partners across campus, launched the Center with the goal of finding potential therapies for the thousands of human diseases for which there is no cure.

“The reorientation of existing therapeutic interventions in the clinical setting has many advantages that significantly reduce the time between discovery and clinical use, including documented safety profiles, reduced regulatory burden, and substantial cost savings.” said George A. Mashour, MD, PhD, co-director of MICHR and founder / executive sponsor of CDR.

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