Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters

Abstract Objectives Antiviral interventions are required to complement vaccination programmes and reduce the global burden of COVID-19. Prior to initiation of large-scale clinical trials, robust preclinical data to support candidate plausibility are required. This work sought to further investigate...

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Published in:Journal of antimicrobial chemotherapy 2024-01, Vol.79 (1), p.172-178
Main Authors: Box, Helen J, Sharp, Joanne, Pennington, Shaun H, Kijak, Edyta, Tatham, Lee, Caygill, Claire H, Lopeman, Rose C, Jeffreys, Laura N, Herriott, Joanne, Neary, Megan, Valentijn, Anthony, Pertinez, Henry, Curley, Paul, Arshad, Usman, Rajoli, Rajith K R, Jochmans, Dirk, Vangeel, Laura, Neyts, Johan, Chatelain, Eric, Escudié, Fanny, Scandale, Ivan, Rannard, Steve, Stewart, James P, Biagini, Giancarlo A, Owen, Andrew
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents - pharmacology
Body Weight
Cricetinae
Humans
Lung
Mesocricetus
Original Research
Probenecid - pharmacology
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Summary:Abstract Objectives Antiviral interventions are required to complement vaccination programmes and reduce the global burden of COVID-19. Prior to initiation of large-scale clinical trials, robust preclinical data to support candidate plausibility are required. This work sought to further investigate the putative antiviral activity of probenecid against SARS-CoV-2. Methods Vero E6 cells were preincubated with probenecid, or control media for 2 h before infection (SARS-CoV-2/Human/Liverpool/REMRQ0001/2020). Probenecid or control media was reapplied, plates reincubated and cytopathic activity quantified by spectrophotometry after 48 h. In vitro human airway epithelial cell (HAEC) assays were performed for probenecid against SARS-CoV-2-VoC-B.1.1.7 (hCoV-19/Belgium/rega-12211513/2020; EPI_ISL_791333, 2020-12-21) using an optimized cell model for antiviral testing. Syrian golden hamsters were intranasally inoculated (SARS-CoV-2 Delta B.1.617.2) 24 h prior to treatment with probenecid or vehicle for four twice-daily doses. Results No observable antiviral activity for probenecid was evident in Vero E6 or HAEC assays. No reduction in total or subgenomic RNA was observed in terminal lung samples (P > 0.05) from hamsters. Body weight of uninfected hamsters remained stable whereas both probenecid- and vehicle-treated infected hamsters lost body weight (P > 0.5). Conclusions These data do not support probenecid as a SARS-CoV-2 antiviral drug.
ISSN:0305-7453
1460-2091
1460-2091
DOI:10.1093/jac/dkad362