Researchers around the world have been searching for ways to cure COVID-19 since the outbreak of the pandemic. While the COVID-19 vaccines are the best way to prevent the disease from spreading, there is a shortage of treatments for those who have been infected. U-M's groundbreaking new study has revealed that several drugs are already available for other purposes, including one dietary supplement. These drug candidates have been proven to reduce or block SARS-CoV2 infections in cells.
This study was published in the Proceedings of the National Academy of Science. It uses artificial intelligence to analyze human cell lines that were infected with the coronavirus. The cells were exposed to more than 1,400 FDA-approved drugs and compounds before and after the virus infection. 17 potential hits were identified. Ten of those hits were new, while seven others were identified in drug repurposing studies.
Jonathan Sexton, Ph.D. Assistant Professor of Internal Medicine at U-M Medical School, and one of the leading authors of the paper, stated that "traditionally, the drug development process takes 10 years -- and we just don’t have a decade." Because of their safety, the therapies we have discovered are well-positioned for phase 2 clinical trials.
In an attempt to replicate SARS-CoV2 infection in the respiratory tract, the team validated 17 candidate compounds in a variety of cells. Nine compounds showed reasonable antiviral activity, including lactoferrin (a protein found in human milk and also available over-the-counter as a dietary supplement).
Sexton stated that lactoferrin was remarkable in its ability to prevent infection. It worked better than any other antibiotics. Sexton also stated that early data suggests this efficacy extends to newer SARS-CoV2 variants, including the highly transmissible Delta.
To determine if the compound can reduce inflammation and viral loads in patients suffering from SARS-CoV2 disease, the team will soon launch clinical trials.
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These trials add to the growing number of ongoing studies on promising repurposed drug candidates. Sexton pointed out that other drug repurposing research has identified compounds with potential effectiveness against SARS-CoV2 over the course the pandemic. He said that the results depend on which cell system was used.
"But, there is an emerging consensus about a subset drugs and those are those that have the highest priority in clinical translation. While we expect the majority of these drugs to fail in humans, there may be some that do.
Surprising results about COVID and certain drugs
The U-M study found that a class called MEK inhibitors, which are usually prescribed for cancer treatment, can worsen SARS/CoV2 infection. This discovery sheds light into how the virus spreads between cells.
People who go in for chemotherapy already have a lower immune response and are at greater risk. Sexton stated that we need to find out if some of these drugs can worsen the disease progression.
He said that the next step is to use electronic medical records to determine if patients taking these drugs have worse COVID-19 results.
This is one of the major discoveries made by the U-M Center for Drug Repurposing, which was founded in November 2019 just as the pandemic started. With partners from campus, the Michigan Institute for Clinical & Health Research was the first to create the Center. The Center was established with the aim of discovering potential treatments for thousands of human diseases.
"Repurposing therapeutic interventions in clinical settings has many benefits that result in significantly shorter time from discovery to clinical usage," stated George A. Mashour MD, PhD, codirector of MICHR, founder/executive sponsorship of the CDR.
The study also included Sexton and Mashour, as well as Jesse Wotring, Ph.D. and Charles Zhang.
