Antiviral effect of alpha-glucosidase inhibitors on viral morphogenesis and binding properties of hepatitis C virus-like particles

The Journal of General Virology
Cynthia ChapelDavid Durantel

Abstract

Hepatitis C virus (HCV) infections are a major public-health concern. New antiviral drugs are needed urgently to complement and improve the efficacy of current chemotherapies. The morphogenesis of HCV represents an interesting, and still unexploited, novel molecular target. alpha-Glucosidase inhibitors derived from the glucose analogue deoxynojirimycin (DNJ) inhibit viral morphogenesis in cellulo via perturbation of the N-glycosylation pathway and hence the misfolding of viral glycoproteins that depend on certain N-glycans for correct folding. Due to the heavy N-glycosylation of HCV glycoproteins, it was hypothesized that such inhibitors would also affect HCV morphogenesis. To study the effect of alpha-glucosidase inhibitors on viral morphogenesis and binding properties, HCV virus-like particles (VLPs) were produced by using baculovirus loaded with HCV structural-protein genes. Here, it is demonstrated that, in the presence of these alpha-glucosidase inhibitors, viral glycoproteins synthesized and retained in the endoplasmic reticulum (i) contain unprocessed, triglucosylated N-glycans, (ii) are impaired in their interaction with calnexin and (iii) are at least partially misfolded. Moreover, it is shown that, although the produc...Continue Reading

References

Mar 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·Q L ChooP J Barr
Jan 1, 1996·Cytotechnology·G W Blissard
Jul 13, 2000·Baillière's Best Practice & Research. Clinical Gastroenterology·T PoynardP Bedossa
Feb 24, 2001·Traffic·I Braakman, E van Anken
Jul 18, 2002·Nature Reviews. Drug Discovery·Raymond A DwekNicole Zitzmann
Aug 6, 2002·Current Opinion in Microbiology·Timothy L Tellinghuisen, Charles M Rice
Aug 7, 2002·Biochemical and Biophysical Research Communications·Norica Branza-NichitaNicole Zitzmann
Sep 27, 2002·The New England Journal of Medicine·Michael W FriedJian Yu
Apr 12, 2003·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Gary L DavisDaniel M Rosenberg
Jun 11, 2004·Annual Review of Biochemistry·Ari Helenius, Markus Aebi
Aug 25, 2004·Gastroenterology Clinics of North America·Cindy J Lai, Norah A Terrault
Sep 4, 2004·Seminars in Liver Disease·Graham R Foster
Oct 28, 2004·Gastroenterology·T Jake Liang, Theo Heller
Nov 9, 2004·Advances in Virus Research·Ralf BartenschlagerThomas Pietschmann
Feb 26, 2005·Seminars in Liver Disease·Jean-Michel Pawlotsky
Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jin ZhongFrancis V Chisari
Jun 11, 2005·Science·Brett D LindenbachCharles M Rice

❮ Previous
Next ❯

Citations

Apr 2, 2010·Antonie van Leeuwenhoek·María D Frade-PérezHéctor M Mora-Montes
Apr 28, 2009·Nature·October M SessionsMariano A Garcia-Blanco
Dec 1, 2007·Nature Reviews. Drug Discovery·Erik De Clercq
Nov 2, 2012·Molekuliarnaia biologiia·A V TimokhovaS N Belzhelarskaia
Mar 21, 2009·American Journal of Respiratory and Critical Care Medicine·Bob LubambaTeresinha Leal
Sep 22, 2012·Human Vaccines & Immunotherapeutics·Qiang Chen, Huafang Lai
Nov 6, 2012·Food Chemistry·Shin-Duk Kim
Sep 17, 2014·The Journal of Antimicrobial Chemotherapy·S HussainJ W McCauley
Nov 19, 2013·Postgraduate Medical Journal·S JyothiS Hackett
Aug 7, 2013·Archives of Disease in Childhood. Education and Practice Edition·S JyothiS Hackett
May 18, 2016·Organic & Biomolecular Chemistry·Ying-Ying SongChu-Yi Yu
Oct 15, 2010·British Journal of Pharmacology·Martin McLaughlin, Koen Vandenbroeck
Jun 6, 2019·Nanomedicine·Noura H Abd EllahHelal F Hetta
Jan 20, 2016·World Journal of Hepatology·Ronik Khachatoorian, Samuel W French
Dec 10, 2016·Critical Reviews in Microbiology·Beatrice Ellen TyrrellNicole Zitzmann
Jan 1, 2013·Current Hepatitis Reports·Gisa Gerold, Thomas Pietschmann
May 8, 2020·Antibiotics·Reuben MaghembeRajni Hatti-Kaul
Jan 1, 2021·Journal of Structural Biology·Munazza Shahid, Syed Shahzad-Ul-Hussan
Aug 10, 2020·Antiviral Research·Lisa Evans DeWaldKelly L Warfield
Jun 16, 2012·Clinical Biochemistry·Bob LubambaTeresinha Leal

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Related Papers

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Masanori IkedaNobuyuki Kato
Proceedings of the National Academy of Sciences of the United States of America
Sharookh B Kapadia, Francis V Chisari
The Journal of Antimicrobial Chemotherapy
Shirit Einav, Jeffrey S Glenn
© 2021 Meta ULC. All rights reserved