دورية أكاديمية
Targeting Endoplasmic Reticulum α-Glucosidase I with a Single-Dose Iminosugar Treatment Protects against Lethal Influenza and Dengue Virus Infections.
| العنوان: | Targeting Endoplasmic Reticulum α-Glucosidase I with a Single-Dose Iminosugar Treatment Protects against Lethal Influenza and Dengue Virus Infections. |
|---|---|
| المؤلفون: | Warfield KL; Emergent BioSolutions, Gaithersburg, Maryland 20879, United States., Alonzi DS; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England, U.K., Hill JC; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England, U.K., Caputo AT; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England, U.K., Roversi P; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England, U.K.; Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 7RH, England, U.K., Kiappes JL; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England, U.K., Sheets N; La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, United States., Duchars M; Emergent BioSolutions, Gaithersburg, Maryland 20879, United States., Dwek RA; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England, U.K., Biggins J; Integrated Biotherapeutics Inc., Gaithersburg, Maryland 20878, United States., Barnard D; Institute for Antiviral Research, Utah State University, Logan, Utah 84322, United States., Shresta S; La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, United States., Treston AM; Emergent BioSolutions, Gaithersburg, Maryland 20879, United States., Zitzmann N; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, England, U.K. |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2020 Apr 23; Vol. 63 (8), pp. 4205-4214. Date of Electronic Publication: 2020 Apr 15. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | alpha-Glucosidases*/metabolism, Dengue/*prevention & control , Endoplasmic Reticulum/*drug effects , Glycoside Hydrolase Inhibitors/*administration & dosage , Influenza, Human/*prevention & control, Animals ; Dengue/drug therapy ; Dengue/enzymology ; Dengue Virus/drug effects ; Dengue Virus/enzymology ; Dose-Response Relationship, Drug ; Endoplasmic Reticulum/enzymology ; Humans ; Influenza, Human/drug therapy ; Influenza, Human/enzymology ; Mice, 129 Strain ; Mice, Inbred BALB C ; Protein Structure, Secondary |
| مستخلص: | Influenza and dengue viruses present a growing global threat to public health. Both viruses depend on the host endoplasmic reticulum (ER) glycoprotein folding pathway. In 2014, Sadat et al. reported two siblings with a rare genetic defect in ER α-glucosidase I (ER Glu I) who showed resistance to viral infections, identifying ER Glu I as a key antiviral target. Here, we show that a single dose of UV-4B (the hydrochloride salt form of N -(9'-methoxynonyl)-1-deoxynojirimycin; MON-DNJ) capable of inhibiting Glu I in vivo is sufficient to prevent death in mice infected with lethal viral doses, even when treatment is started as late as 48 h post infection. The first crystal structure of mammalian ER Glu I will constitute the basis for the development of potent and selective inhibitors. Targeting ER Glu I with UV-4B-derived compounds may alter treatment paradigms for acute viral disease through development of a single-dose therapeutic regime. |
| معلومات مُعتمدة: | 097300/Z/11/Z United Kingdom WT_ Wellcome Trust; 106272/Z/14/Z United Kingdom WT_ Wellcome Trust |
| المشرفين على المادة: | 0 (Glycoside Hydrolase Inhibitors) EC 3.2.1.- (glucosidase I) EC 3.2.1.20 (alpha-Glucosidases) |
| تواريخ الأحداث: | Date Created: 20200402 Date Completed: 20200924 Latest Revision: 20200924 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1021/acs.jmedchem.0c00067 |
| PMID: | 32227946 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4804 |
|---|---|
| DOI: | 10.1021/acs.jmedchem.0c00067 |