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

Box, Helen J, Sharp, Joanne, Pennington, Shaun ORCID: https://orcid.org/0000-0002-7160-6275, Kijak, Edyta, Tatham, Lee, Caygill, Claire H, Lopeman, Rose, Jeffreys, Laura ORCID: https://orcid.org/0000-0002-0607-6116, 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 ORCID: https://orcid.org/0000-0001-6356-6595 and Owen, Andrew (2023) 'Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters'. Journal of Antimicrobial Chemotherapy, Vol 79, Issue 1, pp. 172-178.

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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.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1093/jac/dkad362
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	04 Dec 2023 12:13
Last Modified:	16 Feb 2024 15:48
URI:	https://archive.lstmed.ac.uk/id/eprint/23609

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