Abstract | INTRODUCTION: MATERIALS AND METHODS: Monkey VeroE6 cells and human alveolar basal epithelial A549-ACE2 cells were infected with SARS-CoV-2 in the presence of various concentrations of CPZ. Supernatants were harvested at day 2 and analysed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for the presence of SARS-CoV-2 RNA. Cell viability was assessed in non-infected cells. RESULTS: CPZ was found to have antiviral activity against SARS-CoV-2 in monkey VeroE6 cells, with a half maximal inhibitory concentration (IC50) of 8.2 µM, half maximal cytotoxic concentration (CC50) of 13.5 µM, and selectivity index (SI) of 1.65. In human A549-ACE2 cells, CPZ was also found to have anti-SARS-CoV-2 activity, with IC50 of 11.3 µM, CC50 of 23.1 µM and SI of 2.04. DISCUSSION: Although the measured SI values are low, the IC50 values measured in vitro may translate to CPZ dosages used in routine clinical practice because of the high biodistribution of CPZ in lungs and saliva. Also, the distribution of CPZ in brain could be of interest for treating or preventing neurological and psychiatric forms of COVID-19. CONCLUSIONS: These preclinical findings support clinical investigation of the repurposing of CPZ, a drug with mild side effects, in the treatment of patients with COVID-19.
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Authors | Marion Plaze, David Attali, Matthieu Prot, Anne-Cécile Petit, Michael Blatzer, Fabien Vinckier, Laurine Levillayer, Jeanne Chiaravalli, Florent Perin-Dureau, Arnaud Cachia, Gérard Friedlander, Fabrice Chrétien, Etienne Simon-Loriere, Raphaël Gaillard |
Journal | International journal of antimicrobial agents
(Int J Antimicrob Agents)
Vol. 57
Issue 3
Pg. 106274
(Mar 2021)
ISSN: 1872-7913 [Electronic] Netherlands |
PMID | 33387629
(Publication Type: Journal Article)
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Copyright | Copyright © 2021 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antiviral Agents
- Chlorpromazine
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Topics |
- A549 Cells
- Animals
- Antiviral Agents
(pharmacology)
- Cell Line
- Chlorocebus aethiops
- Chlorpromazine
(pharmacokinetics, pharmacology)
- Drug Repositioning
- Humans
- SARS-CoV-2
(drug effects)
- Tissue Distribution
- Vero Cells
- Virus Replication
(drug effects)
- COVID-19 Drug Treatment
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