Prophylaxis, treatment with probenecid inhibits 'virus replication' in COVID-19, flu, RSV
Probenecid could potentially be used to prevent or treat not only COVID-19, but other respiratory illnesses including influenza and respiratory syncytial virus infection, according to data published in Scientific Reports.
The findings are based on work in animal models and human lung cells conducted by researchers at the University of Georgia, TrippBio Inc., Certara and Florida Atlantic University. Altogether, they suggest that the gout drug inhibits SARS-CoV-2, influenza and RSV replication when used as either a prophylactic or as treatment.
“Scientists around the world are evaluating treatments for COVID-19,” Ralph A. Tripp, PhD, co-owner of the pharmaceutical company TrippBio and professor at the University of Georgia College of Veterinary Medicine, in Athens, told Healio Rheumatology. “Many potential antiviral compounds have been evaluated in vitro, while fewer have been tested in animal models and even fewer have been tested in patients. The FDA has approved Veklury (remdesivir) as the first drug for treatment of COVID-19. Remdesivir failed in clinical trials against Ebola virus but was considered generally safe.”
“Now remdesivir is administered as an injection to treat COVID-19 in hospitalized adults and children,” he added. “Traditional drug discovery pipelines are time- and resource-intensive, and unable to rapidly respond to outbreaks or pandemics. We have performed several genome-wide RNAi screens to discover host genes and pathways co-opted by respiratory viruses and used this data to evaluate repurposed drugs for CoV2, flu and RSV.”
In these virus-host studies, Tripp and colleagues found that probenecid targets a host gene called OAT3, which is used by viruses such as SARS-CoV-2, influenza and RSV to transport and packaging viral proteins in infected cells.
According to the researchers, probenecid works both as a prophylactic prior to virus exposure and as a post-exposure treatment in animal models against SARS-CoV-2 and influenza. The drug is also effective in fighting the RSV in vitro, with in vivo studies in progress.
“We found that that prophylactic or therapeutic treatment with probenecid inhibited SARS-CoV-2, influenza and RSV replication in human lung cells, and in an animal model, in a dose-dependent fashion at nanomolar to micromolar concentrations,” Tripp said. “Importantly, probenecid treatment had no detectable cytotoxicity yet inhibited virus replication.”
A press release issued by the University of Georgia added that, in addition to preventing illness before it starts, probenecid may also increase the efficacy of other treatments. “Probenecid is already used to up the potency of some antibiotics, so it’s possible the medication could work in conjunction with other COVID-19 treatments as well,” read the press release, in part. “Now the researchers are investigating what dosage of probenecid could have the biggest impact fighting viruses in people. TrippBio is set to begin clinical trials of the medication within the year.”