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Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2

Jeffreys, Laura N.; Pennington, Shaun H.; Duggan, Jack; Caygill, Claire H.; Lopeman, Rose C.; Breen, Alastair F.; Jinks, Jessica B.; Ardrey, Alison; Donnellan, Samantha; Patterson, Edward I.; Hughes, Grant L.; Hong, David W.; O'Neill, Paul M.; Aljayyoussi, Ghaith; Owen, Andrew; Ward, Stephen A; Biagini, Giancarlo A

Authors

Laura N. Jeffreys

Shaun H. Pennington

Jack Duggan

Claire H. Caygill

Rose C. Lopeman

Alastair F. Breen

Jessica B. Jinks

Alison Ardrey

Edward I. Patterson

Grant L. Hughes

David W. Hong

Paul M. O'Neill

Ghaith Aljayyoussi

Andrew Owen

Stephen A Ward

Giancarlo A Biagini



Abstract

A key element for the prevention and management of COVID-19 is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer several advantages over monotherapies, including the potential to achieve greater efficacy, the potential to increase the therapeutic index of drugs and the potential to reduce the emergence of drug resistance. Here, we report on the in vitro synergistic interaction between two FDA approved drugs, remdesivir and ivermectin resulting in enhanced antiviral activity against SARS-CoV-2. Whilst the in vitro synergistic activity reported here does not support the clinical application of this combination treatment strategy, due to insufficient exposure of ivermectin in vivo, the data do warrant further investigation. Efforts to define the mechanisms underpinning the observed synergistic action, could lead to the development of novel therapeutic treatment strategies.

Citation

Jeffreys, L. N., Pennington, S. H., Duggan, J., Caygill, C. H., Lopeman, R. C., Breen, A. F., …Biagini, G. A. (2022). Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2. International Journal of Antimicrobial Agents, 59(3), Article 106542. https://doi.org/10.1016/j.ijantimicag.2022.106542

Journal Article Type Article
Acceptance Date Jan 24, 2022
Online Publication Date Jan 31, 2022
Publication Date 2022-03
Deposit Date Feb 15, 2022
Journal International Journal of Antimicrobial Agents
Print ISSN 0924-8579
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 59
Issue 3
Article Number 106542
DOI https://doi.org/10.1016/j.ijantimicag.2022.106542
Keywords SARS-CoV-2, COVID-19, cytopathic activity, CPE, combination therapy, synergy
Public URL http://researchrepository.napier.ac.uk/Output/2845755


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