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

Helen J. Box; Joanne Sharp; Shaun Pennington; Edyta Kijak; Lee Tatham; Claire Caygill; Rose Lopeman; Laura Jeffreys; Joanne Herriott; Megan Neary; Anthony Valentijn; Henry Pertinez; Paul Curley; Usman Arshad; Rajith K.R. Rajoli; Dirk Jochmans; Laura Vangeel; Johan Neyts; Eric Chatelain; Fanny Escudié; Ivan Scandale; Steve Rannard; James P. Stewart; Giancarlo Biagini; Andrew Owen

doi:10.1093/jac/dkad362

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

Helen J. Box, Joanne Sharp, Shaun Pennington, Edyta Kijak, Lee Tatham, Claire Caygill, Rose Lopeman, Laura Jeffreys, Joanne Herriott, Megan Neary, Anthony Valentijn, Henry Pertinez, Paul Curley, Usman Arshad, Rajith K.R. Rajoli, Dirk Jochmans, Laura Vangeel, Johan Neyts, Eric Chatelain, Fanny EscudiéIvan Scandale, Steve Rannard, James P. Stewart, Giancarlo Biagini, Andrew Owen

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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.

Original language	English
Pages (from-to)	172-178
Number of pages	7
Journal	Journal of Antimicrobial Chemotherapy
Volume	79
Issue number	1
DOIs	https://doi.org/10.1093/jac/dkad362
Publication status	Published - 23 Nov 2023

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Box, H. J., Sharp, J., Pennington, S., Kijak, E., Tatham, L., Caygill, C., Lopeman, R., Jeffreys, L., Herriott, J., Neary, M., Valentijn, A., Pertinez, H., Curley, P., Arshad, U., Rajoli, R. K. R., Jochmans, D., Vangeel, L., Neyts, J., Chatelain, E., ... Owen, A. (2023). Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters. Journal of Antimicrobial Chemotherapy, 79(1), 172-178. https://doi.org/10.1093/jac/dkad362

@article{3bd45dd4d58b4fbf90b0036b1fa0f886,

title = "Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters",

abstract = "ObjectivesAntiviral 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. MethodsVero 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. ResultsNo 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). ConclusionsThese data do not support probenecid as a SARS-CoV-2 antiviral drug.",

author = "Box, \{Helen J.\} and Joanne Sharp and Shaun Pennington and Edyta Kijak and Lee Tatham and Claire Caygill and Rose Lopeman and Laura Jeffreys and Joanne Herriott and Megan Neary and Anthony Valentijn and Henry Pertinez and Paul Curley and Usman Arshad and Rajoli, \{Rajith K.R.\} and Dirk Jochmans and Laura Vangeel and Johan Neyts and Eric Chatelain and Fanny Escudi{\'e} and Ivan Scandale and Steve Rannard and Stewart, \{James P.\} and Giancarlo Biagini and Andrew Owen",

year = "2023",

month = nov,

day = "23",

doi = "10.1093/jac/dkad362",

language = "English",

volume = "79",

pages = "172--178",

journal = "Journal of Antimicrobial Chemotherapy",

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Box, HJ, Sharp, J, Pennington, S, Kijak, E, Tatham, L, Caygill, C , Lopeman, R, Jeffreys, L, Herriott, J, Neary, M, Valentijn, A, Pertinez, H, Curley, P, Arshad, U, Rajoli, RKR, Jochmans, D, Vangeel, L, Neyts, J, Chatelain, E, Escudié, F, Scandale, I, Rannard, S, Stewart, JP, Biagini, G & Owen, A 2023, 'Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters', Journal of Antimicrobial Chemotherapy, vol. 79, no. 1, pp. 172-178. https://doi.org/10.1093/jac/dkad362

TY - JOUR

T1 - Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters

AU - Box, Helen J.

AU - Sharp, Joanne

AU - Pennington, Shaun

AU - Kijak, Edyta

AU - Tatham, Lee

AU - Caygill, Claire

AU - Lopeman, Rose

AU - Jeffreys, Laura

AU - Herriott, Joanne

AU - Neary, Megan

AU - Valentijn, Anthony

AU - Pertinez, Henry

AU - Curley, Paul

AU - Arshad, Usman

AU - Rajoli, Rajith K.R.

AU - Jochmans, Dirk

AU - Vangeel, Laura

AU - Neyts, Johan

AU - Chatelain, Eric

AU - Escudié, Fanny

AU - Scandale, Ivan

AU - Rannard, Steve

AU - Stewart, James P.

AU - Biagini, Giancarlo

AU - Owen, Andrew

PY - 2023/11/23

Y1 - 2023/11/23

N2 - ObjectivesAntiviral 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. MethodsVero 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. ResultsNo 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). ConclusionsThese data do not support probenecid as a SARS-CoV-2 antiviral drug.

AB - ObjectivesAntiviral 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. MethodsVero 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. ResultsNo 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). ConclusionsThese data do not support probenecid as a SARS-CoV-2 antiviral drug.

U2 - 10.1093/jac/dkad362

DO - 10.1093/jac/dkad362

M3 - Article

SN - 0305-7453

VL - 79

SP - 172

EP - 178

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 1

ER -

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

Abstract

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