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dc.contributor.authorLi, Zhong
dc.contributor.authorXu, Jimin
dc.contributor.authorLang, Yuekun
dc.contributor.authorWu, Xiangmeng
dc.contributor.authorHu, Saiyang
dc.contributor.authorSamrat, Subodh Kumar
dc.contributor.authorTharappel, Anil M.
dc.contributor.authorKuo, Lili
dc.contributor.authorButler, David
dc.contributor.authorSong, Yongcheng
dc.contributor.authorZhang, Qing-Yu
dc.contributor.authorZhou, Jia
dc.contributor.authorLi, Hongmin
dc.date.accessioned2022-08-04T22:53:32Z
dc.date.available2022-08-04T22:53:32Z
dc.date.issued2022-04
dc.identifier.citationLi, Z., Xu, J., Lang, Y., Wu, X., Hu, S., Samrat, S. K., ... & Li, H. (2022). In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus. Acta Pharmaceutica Sinica B, 12(4), 1662-1670.en_US
dc.identifier.issn2211-3835
dc.identifier.doi10.1016/j.apsb.2021.10.017
dc.identifier.urihttp://hdl.handle.net/10150/665545
dc.description.abstractZika virus (ZIKV) causes significant human diseases without specific therapy. Previously we found erythrosin B, an FDA-approved food additive, inhibited viral NS2B−NS3 interactions, leading to inhibition of ZIKV infection in cell culture. In this study, we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse models. Our results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid model. Although pharmacokinetics studies indicated that erythrosin B had a low absorption profile, mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B, compared to vehicle control. Limited structure−activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B−NS3 interactions, protease activity and antiviral efficacy. In contrast, introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities, suggesting that the isobenzofuran ring is well tolerated for modifications. Cytotoxicity studies indicated that all derivatives are nontoxic to human cells. Overall, our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.en_US
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseasesen_US
dc.language.isoenen_US
dc.publisherElsevier BVen_US
dc.rights© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectFlavivirusen_US
dc.subjectZika virusen_US
dc.subjectDengue virusen_US
dc.subjectAntiviralen_US
dc.subjectProtease inhibitoren_US
dc.subjectErythrosin Ben_US
dc.titleIn vitro and in vivo characterization of erythrosin B and derivatives against Zika virusen_US
dc.typeArticleen_US
dc.contributor.departmentDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizonaen_US
dc.identifier.journalActa Pharmaceutica Sinica Ben_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.piiS2211383521004093
dc.source.journaltitleActa Pharmaceutica Sinica B
dc.source.volume12
dc.source.issue4
dc.source.beginpage1662
dc.source.endpage1670
refterms.dateFOA2022-08-04T22:53:33Z


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© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).