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

Laura Jeffreys; Shaun Pennington; Jack Duggan; Claire Caygill; Rose Lopeman; Alastair Breen; Jess Jinks; Alison Ardrey; Samantha Donnellan; Ian Patterson; Grant Hughes; David W. Hong; Paul M. O'Neill; Ghaith Aljayyoussi; Andrew Owen; Steve Ward; Giancarlo Biagini

doi:10.1016/j.ijantimicag.2022.106542

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

Laura Jeffreys, Shaun Pennington, Jack Duggan, Claire Caygill, Rose Lopeman, Alastair Breen, Jess Jinks, Alison Ardrey, Samantha Donnellan, Ian Patterson, Grant Hughes, David W. Hong, Paul M. O'Neill, Ghaith Aljayyoussi, Andrew Owen, Steve Ward, Giancarlo Biagini

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

14 Citations (Scopus)

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.

Original language	English
Article number	106542
Pages (from-to)	e106542
Journal	International Journal of Antimicrobial Agents
Volume	59
Issue number	3
Early online date	31 Jan 2022
DOIs	https://doi.org/10.1016/j.ijantimicag.2022.106542
Publication status	E-pub ahead of print - 31 Jan 2022

Keywords

Combination therapy
COVID-19
CPE
Cytopathic activity
SARS-CoV-2
Synergy

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10.1016/j.ijantimicag.2022.106542Licence: CC BY

J Antim Agents inpress -Jeffreys2022Accepted author manuscript, 854 KBLicence: CC BY

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Jeffreys, L., Pennington, S., Duggan, J., Caygill, C., Lopeman, R., Breen, A., Jinks, J., Ardrey, A., Donnellan, S., Patterson, I., Hughes, G., Hong, D. W., O'Neill, P. M., Aljayyoussi, G., Owen, A., Ward, S., & Biagini, G. (2022). Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2. International Journal of Antimicrobial Agents, 59(3), e106542. Article 106542. Advance online publication. https://doi.org/10.1016/j.ijantimicag.2022.106542

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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.",

keywords = "Combination therapy, COVID-19, CPE, Cytopathic activity, SARS-CoV-2, Synergy",

author = "Laura Jeffreys and Shaun Pennington and Jack Duggan and Claire Caygill and Rose Lopeman and Alastair Breen and Jess Jinks and Alison Ardrey and Samantha Donnellan and Ian Patterson and Grant Hughes and Hong, \{David W.\} and O'Neill, \{Paul M.\} and Ghaith Aljayyoussi and Andrew Owen and Steve Ward and Giancarlo Biagini",

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Jeffreys, L, Pennington, S, Duggan, J, Caygill, C , Lopeman, R, Breen, A, Jinks, J, Ardrey, A, Donnellan, S, Patterson, I, Hughes, G, Hong, DW, O'Neill, PM, Aljayyoussi, G, Owen, A, Ward, S & Biagini, G 2022, 'Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2', International Journal of Antimicrobial Agents, vol. 59, no. 3, 106542, pp. e106542. https://doi.org/10.1016/j.ijantimicag.2022.106542

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AU - Jeffreys, Laura

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AU - Lopeman, Rose

AU - Breen, Alastair

AU - Jinks, Jess

AU - Ardrey, Alison

AU - Donnellan, Samantha

AU - Patterson, Ian

AU - Hughes, Grant

AU - Hong, David W.

AU - O'Neill, Paul M.

AU - Aljayyoussi, Ghaith

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

Abstract

Keywords

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