ArticleThe Journal of biological chemistry2011
A specific interaction of small molecule entry inhibitors with the envelope glycoprotein complex of the Junín hemorrhagic fever arenavirus.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Molecular organization of the New World arenavirus spike glycoprotein complex.Nature microbiology · 2025Article
- The Lassa Virus Stable Signal Peptide Undergoes a Conformational Change to Aid Viral Fusion.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Screening and Identification of Lassa Virus Entry Inhibitors from a Fragment-Based Drug Discovery Library.Viruses · 2022Article
- Lassa antiviral LHF-535 protects guinea pigs from lethal challenge.Scientific reports · 2022Article
- Discovery of a novel highly potent broad-spectrum heterocyclic chemical series of arenavirus cell entry inhibitors.Bioorganic & medicinal chemistry letters · 2021Article
- Characterizing the Lassa Virus Envelope Glycoprotein Membrane Proximal External Region for Its Role in Fusogenicity.Virologica Sinica · 2021Article
- Screening of Botanical Drugs against Lassa Virus Entry.Journal of virology · 2021Article
- SAR studies of 4-acyl-1,6-dialkylpiperazin-2-one arenavirus cell entry inhibitors.Bioorganic & medicinal chemistry letters · 2019Article
- Identification of a clinical compound losmapimod that blocks Lassa virus entry.Antiviral research · 2019Article
- Identification of Clotrimazole Derivatives as Specific Inhibitors of Arenavirus Fusion.Journal of virology · 2019Article
- Structure-activity relationship optimization for lassa virus fusion inhibitors targeting the transmembrane domain of GP2.Protein & cell · 2019Article
- A potent Lassa virus antiviral targets an arenavirus virulence determinant.PLoS pathogens · 2018Article
- Screening and Identification of Lassa Virus Entry Inhibitors from an FDA-Approved Drug Library.Journal of virology · 2018Article
- Article
- Small-Molecule Fusion Inhibitors Bind the pH-Sensing Stable Signal Peptide-GP2 Subunit Interface of the Lassa Virus Envelope Glycoprotein.Journal of virology · 2016Article
- Hitchhiking on the heptahelical highway: structure and function of 7TM receptor complexes.Nature reviews. Molecular cell biology · 2016Review
- Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor.Journal of virology · 2016Article
- Novel Arenavirus Entry Inhibitors Discovered by Using a Minigenome Rescue System for High-Throughput Drug Screening.Journal of virology · 2015Article
- Small-molecule inhibitors of JC polyomavirus infection.Journal of peptide science : an official publication of the European Peptide Society · 2015Article
- NMR structures and localization of the potential fusion peptides and the pre-transmembrane region of SARS-CoV: Implications in membrane fusion.Biochimica et biophysica acta · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Arenaviruses are responsible for acute hemorrhagic fevers worldwide and are recognized to pose significant threats to public health and biodefense. Small molecule compounds have recently been discovered that inhibit arenavirus entry and protect against lethal infection in animal models. These chemically distinct inhibitors act on the tripartite envelope glycoprotein (GPC) through its unusual stable signal peptide subunit to stabilize the complex against pH-induced activation of membrane fusion in the endosome. Here, we report the production and characterization of the intact transmembrane GPC complex of Junín arenavirus and its interaction with these inhibitors. The solubilized GPC is antigenically indistinguishable from the native protein and forms a homogeneous trimer in solution. When reconstituted into a lipid bilayer, the purified complex interacts specifically with its cell-surface receptor transferrin receptor-1. We show that small molecule entry inhibitors specific to New World or Old World arenaviruses bind to the membrane-associated GPC complex in accordance with their respective species selectivities and with dissociation constants comparable with concentrations that inhibit GPC-mediated membrane fusion. Furthermore, competitive binding studies reveal that these chemically distinct inhibitors share a common binding pocket on GPC. In conjunction with previous genetic studies, these findings identify the pH-sensing interface of GPC as a highly vulnerable target for antiviral intervention. This work expands our mechanistic understanding of arenavirus entry and provides a foundation to guide the development of small molecule compounds for the treatment of arenavirus hemorrhagic fevers.
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Registered trials
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