In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus
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Author
Li, ZhongXu, Jimin
Lang, Yuekun
Wu, Xiangmeng
Hu, Saiyang
Samrat, Subodh Kumar
Tharappel, Anil M.
Kuo, Lili
Butler, David
Song, Yongcheng
Zhang, Qing-Yu
Zhou, Jia
Li, Hongmin
Affiliation
Department of Pharmacology and Toxicology, College of Pharmacy, University of ArizonaIssue Date
2022-04
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Elsevier BVCitation
Li, 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.Journal
Acta Pharmaceutica Sinica BRights
© 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/).Collection Information
This 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.Abstract
Zika 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.Note
Open access journalISSN
2211-3835Version
Final published versionSponsors
National Institute of Allergy and Infectious Diseasesae974a485f413a2113503eed53cd6c53
10.1016/j.apsb.2021.10.017
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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/).