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

Laura Jeffreys, Shaun H Pennington, Jack Duggan, Alastair Breen, Jessica Jinks, Alison Ardrey, Samantha Donnellan, Edward I Patterson, View ORCID ProfileGrant L Hughes, David Hong, Paul M O’Neill, Ghaith Aljayyoussi, Andrew Owen, View ORCID ProfileStephen A Ward, View ORCID ProfileGiancarlo A Biagini
doi: https://doi.org/10.1101/2020.12.23.424232
Laura Jeffreys
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Shaun H Pennington
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Jack Duggan
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Alastair Breen
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Jessica Jinks
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Alison Ardrey
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Samantha Donnellan
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Edward I Patterson
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
2Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Grant L Hughes
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
2Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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  • ORCID record for Grant L Hughes
David Hong
3Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, U.K
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Paul M O’Neill
3Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, U.K
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Ghaith Aljayyoussi
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Andrew Owen
4Department of Pharmacology and Therapeutics, Centre of Excellence in Long-acting Therapeutics (CELT), University of Liverpool, Liverpool, L69 3GE, UK
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Stephen A Ward
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Giancarlo A Biagini
1Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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  • ORCID record for Giancarlo A Biagini
  • For correspondence: giancarlo.biagini@lstmed.ac.uk
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Abstract

A key element to the prevention and management of the COVID-19 pandemic is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer a number of advantages to 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. Combination of agents with antiviral mechanisms of action with immune-modulatory or anti-inflammatory drug is also worthy of investigation. Here, we report on the in vitro synergistic interaction between two FDA approved drugs, remdesivir (RDV) and ivermectin (IVM) resulting in enhanced antiviral activity against SARS-CoV-2, the causative pathogen of COVID-19. These findings warrant further investigations into the clinical potential of this combination, together with studies to define the underlying mechanism.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Joint first authors

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 24, 2020.
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Remdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2
Laura Jeffreys, Shaun H Pennington, Jack Duggan, Alastair Breen, Jessica Jinks, Alison Ardrey, Samantha Donnellan, Edward I Patterson, Grant L Hughes, David Hong, Paul M O’Neill, Ghaith Aljayyoussi, Andrew Owen, Stephen A Ward, Giancarlo A Biagini
bioRxiv 2020.12.23.424232; doi: https://doi.org/10.1101/2020.12.23.424232
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Remdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2
Laura Jeffreys, Shaun H Pennington, Jack Duggan, Alastair Breen, Jessica Jinks, Alison Ardrey, Samantha Donnellan, Edward I Patterson, Grant L Hughes, David Hong, Paul M O’Neill, Ghaith Aljayyoussi, Andrew Owen, Stephen A Ward, Giancarlo A Biagini
bioRxiv 2020.12.23.424232; doi: https://doi.org/10.1101/2020.12.23.424232

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