@article{fdi:010085901,
  title = {{P}re-clinical evaluation of antiviral activity of nitazoxanide against {SARS}-{C}o{V}-2},
  author = {{D}riouch, {J}. {S}. and {C}ochin, {M}. and {T}ouret, {F}. and {P}etit, {P}. {R}. and {G}illes, {M}agali and {M}oureau, {G}. and {B}arth{\'e}l{\'e}my, {K}. and {L}aprie, {C}. and {W}attanakul, {T}. and {C}hotsiri, {P}. and {H}oglund, {R}. {M}. and {T}arning, {J}. and {F}raisse, {L}. and {S}jo, {P}. and {M}owbray, {C}. {E}. and {E}scudi{\'e}, {F}. and {S}cnadale, {I}. and {C}hatelain, {E}. and {L}amballerie de, {X}. and {S}olas, {C}. and {N}ougair{\`e}de, {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {T}o address the emergence of {SARS}-{C}o{V}-2, multiple clinical trials in humans were rapidly started, including those involving an oral treatment by nitazoxanide, despite no or limited pre-clinical evidence of antiviral efficacy. {M}ethods {I}n this work, we present a complete pre-clinical evaluation of the antiviral activity of nitazoxanide against {SARS}-{C}o{V}-2. {F}indings {F}irst, we confirmed the in vitro efficacy of nitazoxanide and tizoxanide (its active metabolite) against {SARS}-{C}o{V}-2. {T}hen, we demonstrated nitazoxanide activity in a reconstructed bronchial human airway epithelium model. {I}n a {SARS}-{C}o{V}-2 virus challenge model in hamsters, oral and intranasal treatment with nitazoxanide failed to impair viral replication in commonly affected organs. {W}e hypothesized that this could be due to insufficient diffusion of the drug into organs of interest. {I}ndeed, our pharmacokinetic study confirmed that concentrations of tizoxa-nide in organs of interest were always below the in vitro {EC}50. {I}nterpretation {T}hese preclinical results suggest, if directly applicable to humans, that the standard formulation and dosage of nitazoxanide is not effective in providing antiviral therapy for {C}ovid-19. {F}unding {T}his work was supported by the {F}ondation de {F}rance "call {FLASH} {COVID}-19 ", project {TAMAC}, by "{I}nstitut national de la sante? et de la recherche me?dicale " through the {REACT}ing ({RE}search and {ACT}ion targeting emerging infectious diseases), by {REACTING}/{ANRS} {MIE} under the agreement {N}o. 21180 ('{A}ctivite? des mole?cules antivirales dans le mod?ele hamster'), by {E}uropean {V}irus {A}rchive {G}lobal ({EVA} 213 {GLOBAL}) funded by the {E}uropean {U}nion's {H}orizon 2020 research and innovation program under grant agreement {N}o. 871029 and {DND}i under sup-port by the {W}ellcome {T}rust {G}rant ref: 222489/{Z}/21/{Z} through the {COVID}-19 {T}herapeutics {A}ccelerator ".},
  keywords = {{COVID}-19 ; {SARS}-{C}o{V}-2 ; {A}ntiviral therapy ; {P}re-clinical research ; {N}itazoxanide ; {A}nimal model},
  booktitle = {},
  journal = {{E}biomedicine},
  volume = {82},
  numero = {},
  pages = {104148 [16 p.]},
  ISSN = {2352-3964},
  year = {2022},
  DOI = {10.1016/j.ebiom.2022.104148},
  URL = {https://www.documentation.ird.fr/hor/fdi:010085901},
}