In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus.

Autor:	Li Z; Department of Pharmacology and Toxicology, College of Pharmacy, Tucson, AZ 85721-0207, USA.; Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA., Xu J; Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA., Lang Y; Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA., Wu X; Department of Pharmacology and Toxicology, College of Pharmacy, Tucson, AZ 85721-0207, USA., Hu S; Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA., Samrat SK; Department of Pharmacology and Toxicology, College of Pharmacy, Tucson, AZ 85721-0207, USA.; Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA., Tharappel AM; Department of Pharmacology and Toxicology, College of Pharmacy, Tucson, AZ 85721-0207, USA.; Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA., Kuo L; Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA., Butler D; The Neural Stem Cell Institute, Rensselaer, NY 12144, USA., Song Y; Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA., Zhang QY; Department of Pharmacology and Toxicology, College of Pharmacy, Tucson, AZ 85721-0207, USA., Zhou J; Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA., Li H; Department of Pharmacology and Toxicology, College of Pharmacy, Tucson, AZ 85721-0207, USA.; Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.
Jazyk:	angličtina
Zdroj:	Acta pharmaceutica Sinica. B [Acta Pharm Sin B] 2022 Apr; Vol. 12 (4), pp. 1662-1670. Date of Electronic Publication: 2021 Oct 22.
DOI:	10.1016/j.apsb.2021.10.017
Abstrakt:	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 . (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)
Databáze:	MEDLINE
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