Remdesivir–ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2
Laura N. Jeffreys, Shaun H. Pennington, Jack Duggan, Claire H Caygill, Rose C. Lopeman, Alastair F. Breen, Jessica Jinks, Alison Ardrey, Samantha Donnellan, 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 coronavirus disease 2019 is the development of effective therapeutics. Drug combination strategies offer several advantages over monotherapies. They have the potential to achieve greater efficacy, to increase the therapeutic index of drugs and to reduce the emergence of drug resistance. We assessed the in vitro synergistic interaction between remdesivir and ivermectin, both approved by the US Food and Drug Administration, and demonstrated enhanced antiviral activity against severe acute respiratory syndrome coronavirus-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 treatment strategies.