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

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., Jinks, J. B., Ardrey, A., Donnellan, S., Patterson, E. I., Hughes, G. L., Hong, D. W., O'Neill, P. M., Aljayyoussi, G., Owen, A., Ward, S. A., & 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
• Publicly Available Date: Jun 26, 2023
• 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