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. 2020 Aug:145:104228.
doi: 10.1016/j.micpath.2020.104228. Epub 2020 Apr 25.

In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect

Julien Andreani  1 , Marion Le Bideau  1 , Isabelle Duflot  1 , Priscilla Jardot  1 , Clara Rolland  1 , Manon Boxberger  1 , Nathalie Wurtz  1 , Jean-Marc Rolain  1 , Philippe Colson  1 , Bernard La Scola  2 , Didier Raoult  3
Affiliations

In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect

Julien Andreani et al. Microb Pathog. 2020 Aug.

Abstract

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.

Keywords: 2019-nCoV; Azithromycin; COVID-19; Hydroxychloroquine; SARS-CoV-2; Vero E6.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Observations of infected cells resistant or not to viral replication after inoculation of SARS-CoV 2 strain IHUMI-3 at MOI 0.25.
Fig. 2
Fig. 2
Effect of hydroxychloroquine and azithromycin association on SARS-CoV 2 replication. 2A. Delta Ct between 0 and 60 h post infection. Ordered axis represents the variation of delta cycle-thresholds obtained by RT-PCR between H0 and H60 for each condition. Each point represents data obtained for one well. Number of replicates was indicated for each conditions are A10H5 n = 16, A10H2 n = 5, A10H1 n = 5, A5H5 n = 15, A5H2 n = 5, A5H1 n = 3, A2H5 n = 3, A2H2 n = 3, A2H1 n = 3 and n = 13 for the positive control. Median and interquartile range were indicated for each condition. *** represent significant results under p < 0,0005. Others are not significant compared to the control. 2B. Percentage of inhibition as compared to control by the combinations of 5 μM of hydroxychloroquine associated with 5 or 10 μM for azithromycin. Data represent the mean ± SD, representing three independent experiments conducted at least in triplicate.
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