Infectious Disease

Prophylaxis, treatment with probenecid inhibits “virus replication” in COVID-19, influenza, RSV

September 13, 2021

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Tripp and co-authors David E. Martin, PharmD, Kathy Blahunka, PharmD, and Richard Still, all of TrippBio, and Fred D. Sancilio, PhD, MS, of TrippBio and Florida Atlantic University, indicate ownership of TrippBio.

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Probenecid could potentially be used not only to prevent or treat COVID-19, but also to other respiratory diseases such as influenza and respiratory syncytial virus infections, according to data published in Scientific Reports.

The results are based on work on animal models and human lung cells by researchers from the University of Georgia, TrippBio Inc., Certara and Florida Atlantic University. Overall, they suggest that the gout drug inhibits the replication of SARS-CoV-2, influenza, and RSV when used either prophylactically or as a treatment.

According to the data, probenecid could potentially be used not only to prevent or treat COVID-19, but also to other respiratory diseases such as influenza and respiratory syncytial virus infections.

“Scientists around the world are evaluating treatments for COVID-19” Ralph A. Tripp, PhD, Co-owner of pharmaceutical company TrippBio and a professor in the College of Veterinary Medicine at the University of Georgia in Athens, said Healio Rheumatology. “Many potential antiviral compounds have been evaluated in vitro, while fewer have been tested in animal models and even fewer in patients. The FDA approved Veklury (Remdesivir) as the first drug to treat COVID-19. Remdesivir failed in clinical trials against the Ebola virus, but was considered generally safe. ”

“Now remdesivir is being given as an injection to treat COVID-19 in hospitalized adults and children,” he added. “Traditional drug discovery pipelines are time and resource intensive and incapable of reacting quickly to outbreaks or pandemics. We performed multiple genome-wide RNAi screenings to discover host genes and pathways co-opted by respiratory viruses, and used these data to evaluate reused drugs for CoV2, influenza, and RSV. “

In these virus-host studies, Tripp and colleagues found that probenecid targets a host gene called OAT3, which is used by viruses like SARS-CoV-2, influenza, and RSV to transport and deliver viral proteins in infected cells pack.

According to the researchers, probenecid works both as a prophylaxis before virus exposure and as a post-exposure treatment in animal models against SARS-CoV-2 and influenza. The drug is also effective in combating RSV in vitro, with in vivo studies ongoing.

“We found that this prophylactic or therapeutic treatment with probenecid inhibited the replication of SARS-CoV-2, influenza and RSV in human lung cells and in an animal model in a dose-dependent manner at nanomolar to micromolar concentrations,” said Tripp. “It is important that the probenecid treatment had no detectable cytotoxicity, but inhibited virus replication.”

A University of Georgia press release added that probenecid may make other treatments more effective in addition to preventing disease. “Probenecid is already being used to increase the effectiveness of some antibiotics, so it is possible that the drug may also work in conjunction with other COVID-19 treatments,” the press release said in part. “Now the researchers are investigating which dosage of probenecid could have the greatest effect in fighting viruses in humans. TrippBio will begin clinical trials of the drug later this year. “

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COVID-19 and rheumatology

COVID-19 and rheumatology

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