ArticleAntimicrobial agents and chemotherapy2015
Inhibition of endoplasmic reticulum-resident glucosidases impairs severe acute respiratory syndrome coronavirus and human coronavirus NL63 spike protein-mediated entry by altering the glycan processing of angiotensin I-converting enzyme 2.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 72 citations in OpenAlex.
- Randomized single oral dose phase 1 study of safety, tolerability, and pharmacokinetics of Iminosugar UV-4 Hydrochloride (UV-4B) in healthy subjects.PLoS neglected tropical diseases · 2022Trial
- Risk Factors for Poor Outcomes of Diabetes Patients With COVID-19: A Single-Center, Retrospective Study in Early Outbreak in China.Frontiers in endocrinology · 2020Trial
- Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Expanding horizons of iminosugars as broad-spectrum anti-virals: mechanism, efficacy and novel developments.Natural products and bioprospecting · 2024Review
- Characterization of CCoV-HuPn-2018 spike protein-mediated viral entry.Journal of virology · 2023Article
- Molecular mechanisms of human coronavirus NL63 infection and replication.Virus research · 2023Review
- The Development of Pharmacophore Models for the Search of New Natural Inhibitors of SARS-CoV-2 Spike RBD-ACE2 Binding Interface.Molecules (Basel, Switzerland) · 2022Article
- Coronavirus Infection-Associated Cell Death Signaling and Potential Therapeutic Targets.Molecules (Basel, Switzerland) · 2021Review
- Analysis of the Role of N-Linked Glycosylation in Cell Surface Expression, Function, and Binding Properties of SARS-CoV-2 Receptor ACE2.Microbiology spectrum · 2021Article
- Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications.Engineering (Beijing, China) · 2021Article
- Longitudinal proteomic profiling provides insights into host response and proteome dynamics in COVID-19 progression.Proteomics · 2021Article
- Targeting the glycans: A paradigm for host-targeted and COVID-19 drug design.Journal of cellular and molecular medicine · 2021Review
- Exploring the Role of Glycans in the Interaction of SARS-CoV-2 RBD and Human Receptor ACE2.Viruses · 2021Article
- Article
- Structural insights of key enzymes into therapeutic intervention against SARS-CoV-2.Journal of structural biology · 2021Review
- N-Glycan Modification in Covid-19 Pathophysiology: In vitro Structural Changes with Limited Functional Effects.Journal of clinical immunology · 2021Article
- ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: the saga continues.Human genomics · 2021Review
- Decoding the silent walk of COVID-19: Halting its spread using old bullets.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Scrutinizing Coronaviruses Using Publicly Available Bioinformatic Tools: The Viral Structural Proteins as a Case Study.Frontiers in molecular biosciences · 2021Review
- Environmentally-inducedTheranostics · 2021Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Endoplasmic reticulum (ER)-resident glucosidases I and II sequentially trim the three terminal glucose moieties on the N-linked glycans attached to nascent glycoproteins. These reactions are the first steps of N-linked glycan processing and are essential for proper folding and function of many glycoproteins. Because most of the viral envelope glycoproteins contain N-linked glycans, inhibition of ER glucosidases with derivatives of 1-deoxynojirimycin, i.e., iminosugars, efficiently disrupts the morphogenesis of a broad spectrum of enveloped viruses. However, like viral envelope proteins, the cellular receptors of many viruses are also glycoproteins. It is therefore possible that inhibition of ER glucosidases not only compromises virion production but also disrupts expression and function of viral receptors and thus inhibits virus entry into host cells. Indeed, we demonstrate here that iminosugar treatment altered the N-linked glycan structure of angiotensin I-converting enzyme 2 (ACE2), which did not affect its expression on the cell surface or its binding of the severe acute respiratory syndrome coronavirus (SARS-CoV) spike glycoprotein. However, alteration of N-linked glycans of ACE2 impaired its ability to support the transduction of SARS-CoV and human coronavirus NL63 (HCoV-NL63) spike glycoprotein-pseudotyped lentiviral particles by disruption of the viral envelope protein-triggered membrane fusion. Hence, in addition to reducing the production of infectious virions, inhibition of ER glucosidases also impairs the entry of selected viruses via a post-receptor-binding mechanism.
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