In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect
Julien Andreani, Marion Le Bideau, Isabelle Duflot, Priscilla Jardot, Clara Rolland, Manon Boxberger, Nathalie Wurtz, Jean-Marc Rolain, Philippe Colson, Bernard La Scola, Didier Raoult
Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with high morbidity and mortality. As there are currently no effective drugs targeting this virus, drug repurposing represents a short-term strategy to treat millions of infected patients at low costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it showed efficacy, especially when combined with azithromycin in a preliminary clinical trial. Here we demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.
Author statement Virus culture and drug testing: JA, ML, ID, NW; Molecular biology testing: PJ, CR, MB; Analyzed the results: JA, JMR, PC, BL, DR; Wrote the manuscript: JA, BL; Conceived the study: BL, DR. Pictures were captured on ZEISS AxioCam ERC 5s, 58 h post infection. Magnitude X200.3A-B-C. overview of the monolayer in each well for the condition of azithromycin 5 μM associated with hydroxychloroquine at 5 μM, 3D. Negative control well and 3E. Positive control well. 1F. Observation was done 48 h post infection by the SARS-CoV 2 strain IHUMI-3 for the viral stock production. Magnitude X400.
Declaration of competing interest Authors would like to declare that Didier Raoult is a consultant in microbiology for Hitachi High-Tech Corporation. Funding sources had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The others authors declare no conflict of interest.
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