Probenecid Inhibits SARS-CoV-2 Replication

With widespread of COVID-19, vaccines are the only key to the pandemic. At present, the treatment focuses on palliative support, an antiviral drug, and vaccines. The host genes were identified using high-throughput screening (HTS) to know about the RNA replication. The organic anion transporter 3 (OAT3) gene, present in the kidney and lungs allow the transport of anions and certain antibiotics. Probenecid, a therapeutic agent, has been earlier reported to increase antibiotic activity.

This drug, Probenecid can be used as a repurposing antiviral drug as it inhibits OAT313, decreasing ACE2 expression and is readily available. The drug activity for in vitro studies has been shown to reduce the Replication of the influenza virus in mice. Additionally, the study was undertaken to know about the inhibitory concentration (IC50) for normal human bronchoepithelial (NHBE) cells and Vero E6 cells Before and after SARS-CoV-2 and the B.1.1.7 variant infection. The Probenecid treatment resulted in a drastic decrease in virus replication by 60% in NHBE cells and 90% in Vero E6 cells.

The research on Hamster with SARS-CoV-2 infection was suppressed while treating with probenecid, as lung virus titers. Hence, the drug Probenecid inhibits the SARS-CoV-2 variant of concern (VOC) and the pharmacological blocking of OAT3 is also reported safe in humans. The oral dose reports 50 fold higher than the protein binding, altered for IC90 in 24hrs. Thus, the drug Probenecid possesses a clinical efficacy and controls the upsurge of coronavirus infections in the future.

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Ref Link: 10.1101/2021.05.21.445119