Причем хомячкам для эффекта досаточно было одной дозы из расчета, меньшей чем допустимые ФДА 2 гр в день.
Авторы полагают, что нужно бы провести клинические испытания пробенецида для лечения ковида. То, что это давно и хорошо известное лекарство- только плюс.
We determined the IC50for Vero E6 cells and normal human bronchoepithelial (NHBE) cells treated beforeand at the time of infection with SARS-CoV-2and the B.1.1.7 variant.The results showed probenecid treatment blocked SARS-CoV-2 replication(plaque formation)in Vero E6 cells or NHBE cells treated with different concentrations of probenecid, i.e. 0.00001 -100 uM.We also evaluated lungviral load in hamsters on days 0, 3, and 7 pi withSARS-CoV-2 using both a tissue culture infectious dose-50 (TCID50) assay and a virus plaque assay todeterminethe number of plaque-forming units (PFU). Hamsters were treated with probenecid 24hbeforeinfection (prophylaxis), or 48hpost-infection (post-treatment)with doses of 2 mg/kg and 200 mg/kg. Hamsters treated with probenecid haddramatically reduced lung virus titers, i.e. a 5-log reduction of virus compared to the controls thatwere approximately 109logs of the virus. We performed a probenecid pharmacokineticmodeling and simulation study comparing 600 mg twice daily,900 mg twice daily, or1800 mg once daily.The model predicted that theplasma concentrations of probenecid would exceed the protein bindingadjusted IC90 value at all timepointsthroughouttherapy. The doses evaluated by the PKmodel werebelow the maximum allowable FDA-approved dose of 2 grams/day and should have no substantial side effects.Together, these data strongly support the potential for probenecid to provide a robust antiviral response against SARS-CoV-2.
Probenecidhas inhibitory effectsonRNAvirusesspecifically influenza10and respiratory syncytial virus (RSV) (data not shown). Probenecid increases uric acid excretion in the urine and has been safely used to treatgout and hyperuricemia22,23, and hasminimal adverse effectsbut may cause mild symptoms such as nausea, or loss of appetite14.Probenecid has several pharmacological targets including blocking pannexins that underlietransmembrane channel function24,25and decreasingACE2 expression26,27.Themajor advantagesof probenecid are that it is an FDA-approved therapeutic drug that has been on the market for >50 years, it can be administeredorallywith favorable pharmacokinetics, it operates at the host cell level,is refractory to viral mutation, andhas the potential to treat multiple other viruses. Further, our data suggest that initiation of post-treatment following infection in mammalian cells, hamsters, and humans results in infection remarkably reducedSARS-CoV-2 replication, particularly in the lung target organ.