Published: 20th August 2021
AI helps identify drugs that can kill SARS-CoV-2 in cells
The team validated the 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
Scientists have used artificial intelligence (AI) to identify several drug contenders already in use for other purposes including one dietary supplement that can block or reduce SARS-CoV-2 infection in cells. The study, published in the journal Proceedings of the National Academy of Science, used AI-powered image analysis of human cell lines during infection with SARS-CoV-2, the virus that causes COVID-19.
The cells were treated with more than 1,400 individual US Food and Drug Administration (FDA) approved drugs and compounds, either before or after viral infection, and screened, resulting in 17 potential hits. Ten of those hits were newly recognised, with seven identified in previous drug repurposing studies, including remdesivir, which is one of the few FDA-approved therapies for COVID-19 in hospitalised patients. "Traditionally, the drug development process takes a decade -- and we just don't have a decade," said Jonathan Sexton, an assistant professor at the University of Michigan (U-M) Medical School in the US. "The therapies we discovered are well positioned for phase 2 clinical trials because their safety has already been established," said Sexton, one of the senior authors on the research paper.
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.
Early data suggests this efficacy extends even to newer variants of SARS-CoV-2, including the highly transmissible Delta variant, the researchers said. 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. The trials are adding to the list of ongoing studies of promising repurposed drugs, the researchers said. The team noted that over the course of the pandemic, other drug repurposing studies have identified different compounds with potential efficacy against SARS-CoV2. "The results seem to be dependent on what cell system is used," Sexton said. "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," he said.
The study also identified a class of compounds called MEK-inhibitors, typically prescribed to treat cancer, that appear to worsen SARS-CoV2 infection. "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.