1. Introduction
death, gout, Infection, deaths, coronavirus disease 2019
VIRUS, CORONAVIRUS DISEASE 2019, ANTIVIRAL DRUGS, CORONAVIRUS, GOUT, SEVERE ACUTE RESPIRATORY SYNDROME, INFECTION
Probenecid is an orally bioavailable, uricosuric agent that was first approved in 1951 for the treatment of gout, but was later found to have potent, broad-spectrum antiviral activity against several respiratory viruses including SARS-CoV-2. We conducted a phase 2 randomized, placebo-controlled, single-blind, dose-range finding study in non-hospitalized patients with symptomatic, mild-to-moderate COVID-19. Patients were randomly assigned in a 1:1:1 ratio to receive either 500 mg of probenecid, 1000 mg of probenecid, or a matching placebo every 12 h for five days. The patients’ COVID-19 viral load hospitalization, or death from any cause through day 28, as well as safety, were evaluated. COVID-19-related symptoms were assessed at baseline, and on days 3, 5, 10, 15, and 28. The primary endpoints of the study were time to first negative SARS-CoV-2 viral test (or viral clearance) and the proportion of patients that were symptom-free at day 5. A total of 75 patients were randomized, with 25 patients in each group. All of the patients completed the study as planned with no hospitalizations or deaths being reported. The median time to viral clearance was significantly shorter for the probenecid 1000 mg group than for placebo (7 days vs. 11 days, respectively; Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in coronavirus disease 2019 (COVID-19) was first reported in 2019 [The evolving nature of SARS-CoV-2 variants emphasizes the need to identify drug treatments that are safe, effective, and refractory to developing drug resistance. Antiviral drugs either target the virus or cellular components which are required for virus replication. Directly targeting the virus can lead to a narrow spectrum of antiviral activity and the likelihood of developing viral mutations and drug resistance. In contrast, antiviral drugs that target the host cell pathways that are usurped by viruses for replication are more likely to be broad-spectrum and inhibit the replication of multiple viruses. Traditional drug discovery pipelines are time- and resource-intensive but bridging high-throughput screening (HTS) with host gene silencing makes it possible to discover host pathways which are used by viruses for their replication [Probenecid was initially developed to decrease the renal clearance of penicillin and increase plasma concentrations [