Drug repurposing study uses live virus to identify 30 potential COVID-19 candidates

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With no vaccine or antiviral therapeutic agent available for COVID-19 treatment, there is an urgent need to identify novel measures for its treatment and prevention. Since vaccine development could take well over a year, and novel treatment even longer, researchers are looking to drug repurposing as another solution.

To this end, an international collaborative research team conducted a large-scale drug repurposing survey to identify existing drugs that prevent the COVID-19 virus from replicating. The study, recently uploaded to BioRxiv, describes the discovery of 30 candidates that could be used to successfully treat COVID-19.

The team consisted of scientists from the Sanford Burnham Prebys Medical Discovery Institute, Scripps Research Institute, University of California San Diego, University of California Los Angeles (all CA, USA), The University of Hong Kong (China), University of Vienna (Austria), Texas Biomedical Research Institute (TX, USA) and Icahn School of Medicine at Mount Sinai (NY, USA).

“We believe this is one of the first comprehensive drug screens using the live SARS-CoV-2 virus, and our hope is that one or more of these drugs will save lives while we wait for a vaccine for COVID-19,” remarked senior author Sumit Chanda (Sanford Burnham Prebys). “Many drugs identified in this study – most of which are new to the COVID-19 research community – can begin clinical trials immediately or in a few months after additional testing.”

In order to identify the drugs, the researchers conducted a high-throughput analysis of the ReFRAME drug repurposing collection, a library of over 12,000 existing drugs that have already achieved FDA approval for other purposes.

After using the live SARS-CoV-2 virus to test every compound, the team discovered 300 drugs that could stop the virus from replicating. Utilizing molecular tools such as PCR and immunofluorescence microscopy, the researchers were then able to determine the 30 most effective candidates.

Of the 30 drugs identified, only three were already under evaluation for use in COVID 19, meaning the researchers identified 27 novel candidates that could be repurposed for COVID-19 treatment. Further, for the three candidates already under clinical evaluation, the results from this study reaffirmed their potential and provided support for the continuation of their clinical trials.

Out of all of the candidates, the researchers identified four drugs, aplimod, MLN-3897, BY-825 and ONO5334, which they believe to be the most promising candidates for near-term COVID-19 treatment as they have already been shown to be effective at the required doses in clinical trials for other diseases.

Although each drug identified requires further evaluation for its effectiveness in human COVID-19 patients before broad use, this study has provided a significant number of novel potential treatment routes. Additionally, the study has highlighted the value drug repurposing has in a pandemic.

“For us, the starting point for finding any new antiviral drug is to measure its ability to block viral replication in the lab,” explained Chanda. “Since the drugs we identified in this study have already been tested in humans and proven safe, we can leapfrog over the more than half decade of studies normally required to get approval for human use.”

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Sources: Riva L, Yan S, Yin X et al. A large-scale drug repositioning survey for SARS-CoV-2 antivirals. BioRxiv doi:10.1101/2020.04.16.044016 (2020) (preprint); www.sbpdiscovery.org/news/researchers-use-live-virus-to-identify-30-existing-drugs-could-treat-covid-19

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