Iminosugar antivirals: the therapeutic sweet spot

被引:82
作者
Alonzi, Dominic S. [1 ]
Scott, Kathryn A. [1 ]
Dwek, Raymond A. [1 ]
Zitzmann, Nicole [1 ]
机构
[1] Univ Oxford, Oxford Glycobiol Inst, Dept Biochem, South Parks Rd, Oxford OX1 3QU, England
关键词
HEPATITIS-C VIRUS; ER-ASSOCIATED DEGRADATION; GLUCOSE-GLYCOPROTEIN-GLUCOSYLTRANSFERASE; SUGAR N-BUTYLDEOXYNOJIRIMYCIN; ENDOPLASMIC-RETICULUM; QUALITY-CONTROL; MISFOLDED GLYCOPROTEINS; RAT-LIVER; INTERMEDIATE COMPARTMENT; INFLUENZA HEMAGGLUTININ;
D O I
10.1042/BST20160182
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Many viruses require the host endoplasmic reticulum protein-folding machinery in order to correctly fold one or more of their glycoproteins. Iminosugars with glucose stereochemistry target the glucosidases which are key for entry into the glycoprotein folding cycle. Viral glycoproteins are thus prevented from interacting with the protein-folding machinery leading to misfolding and an antiviral effect against a wide range of different viral families. As iminosugars target host enzymes, they should be refractory to mutations in the virus. Iminosugars therefore have great potential for development as broadspectrum antiviral therapeutics. We outline the mechanism giving rise to the antiviral activity of iminosugars, the current progress in the development of iminosugar antivirals and future prospects for this field.
引用
收藏
页码:571 / 582
页数:12
相关论文
共 83 条
[41]   Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial [J].
Low, Jenny G. ;
Sung, Cynthia ;
Wijaya, Limin ;
Wei, Yuan ;
Rathore, Abhay P. S. ;
Watanabe, Satoru ;
Tan, Boon Hian ;
Toh, Liying ;
Chua, Lion Tee ;
Hou, Yan'an ;
Chow, Angelia ;
Howe, Shiqin ;
Chan, Wing Ki ;
Tan, Kah Hin ;
Chung, Jasmine S. ;
Cherng, Benjamin P. ;
Lye, David C. ;
Tambayah, Paul A. ;
Ng, Lee Ching ;
Connolly, John ;
Hibberd, Martin L. ;
Leo, Yee Sin ;
Cheung, Yin Bun ;
Ooi, Eng Eong ;
Vasudevan, Subhash G. .
LANCET INFECTIOUS DISEASES, 2014, 14 (08) :706-715
[42]   The Conformational Properties of the Glc3Man Unit Suggest Conformational Biasing within the Chaperone-assisted Glycoprotein Folding Pathway [J].
Mackeen, Mukram M. ;
Almond, Andrew ;
Deschamps, Michael ;
Cumpstey, Ian ;
Fairbanks, Antony J. ;
Tsang, Clarence ;
Rudd, Pauline M. ;
Butters, Terry D. ;
Dwek, Raymond A. ;
Wormaldl, Mark R. .
JOURNAL OF MOLECULAR BIOLOGY, 2009, 387 (02) :335-347
[43]   Hepatitis B virus (HBV) envelope glycoproteins vary drastically in their sensitivity to glycan processing: Evidence that alteration of a single N-linked glycosylation site can regulate HBV secretion [J].
Mehta, A ;
Lu, XY ;
Block, TM ;
Blumberg, BS ;
Dwek, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (05) :1822-1827
[44]   Cellular effects of deoxynojirimycin analogues: inhibition of N-linked oligosaccharide processing and generation of free glucosylated oligosaccharides [J].
Mellor, HR ;
Neville, DCA ;
Harvey, DJ ;
Platt, FM ;
Dwek, RA ;
Butters, TD .
BIOCHEMICAL JOURNAL, 2004, 381 :867-875
[45]   EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin [J].
Oda, Y ;
Hosokawa, N ;
Wada, I ;
Nagata, K .
SCIENCE, 2003, 299 (5611) :1394-1397
[46]   EDEM1 regulates ER-associated degradation by accelerating de-mannosylation of folding-defective polypeptides and by inhibiting their covalent aggregation [J].
Olivari, Silvia ;
Cali, Tito ;
Salo, Kirsi E. H. ;
Paganetti, Paolo ;
Ruddock, Lloyd W. ;
Molinari, Maurizio .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 349 (04) :1278-1284
[47]   CARBOHYDRATES CONTAINING NITROGEN OR SULFUR IN HEMIACETAL RING [J].
PAULSEN, H .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 1966, 5 (05) :495-&
[48]   Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells [J].
Perera, Rushika ;
Riley, Catherine ;
Isaac, Giorgis ;
Hopf-Jannasch, Amber S. ;
Moore, Ronald J. ;
Weitz, Karl W. ;
Pasa-Tolic, Ljiljana ;
Metz, Thomas O. ;
Adamec, Jiri ;
Kuhn, Richard J. .
PLOS PATHOGENS, 2012, 8 (03)
[49]  
PLATT FM, 1994, J BIOL CHEM, V269, P8362
[50]   Malectin Forms a Complex with Ribophorin I for Enhanced Association with Misfolded Glycoproteins [J].
Qin, Sheng-Ying ;
Hu, Dan ;
Matsumoto, Kana ;
Takeda, Koh ;
Matsumoto, Naoki ;
Yamaguchi, Yoshiki ;
Yamamoto, Kazuo .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (45) :38080-38089