Grant: Operating Grant: COVID-19 - Project Grant

The ongoing pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 has posed an unprecedented health and economic threat worldwide. Despite the intense research since its outbreak, there is currently no effective treatment or vaccine for this disease. This project focuses on the development of a novel therapeutic for COVID-19 by drug repositioning. Probenecid, under the brand name Probalan, is a medication that is primarily used in treating gout by increasing uric acid excretion in the urine. We have recently made exciting observations that probenecid potently inhibits infection of two different but related families of RNA viruses, i.e., corona- and entero- viruses. Moreover, unlike some anti-viral drugs that may cause severe cardiotoxicity, probenecid actually reduces cardiovascular risks associated with decreased inflammatory response. Based on these preliminary data and the proven anti-inflammatory role of Probenecid, we postulate that Probenecid is a very attractive drug candidate for COVID-19 treatment by suppressing SARS-CoV-2 replication and alleviating disease-associated systemic and lung inflammation. To test this hypothesis, we propose two aims: (1) evaluate the potential of repurposing Probenecid for COVID-19 treatment using cell and mouse models; and (2) define the underlying anti-viral mechanism of Probenecid. If successful, the significance of this study and the follow-up clinical trial will be huge for patients with COVID-19.