ArticleProceedings of the National Academy of Sciences of the United States of America2013
Host-rabies virus protein-protein interactions as druggable antiviral targets.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 68 citations in OpenAlex.
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- A viral assembly inhibitor blocks SARS-CoV-2 replication in airway epithelial cells.Communications biology · 2024Article
- Protein Assembly Modulation: A New Approach to Amyotrophic Lateral Sclerosis (ALS) Therapeutics.Journal of experimental neurology · 2024Article
- A Pan-Respiratory Antiviral Chemotype Targeting a Host Multi-Protein Complex.bioRxiv : the preprint server for biology · 2023Article
- A Robust Phenotypic High-Throughput Antiviral Assay for the Discovery of Rabies Virus Inhibitors.Viruses · 2023Article
- A Novel Viral Assembly Inhibitor Blocks SARS-CoV-2 Replication in Airway Epithelial Cells.Research square · 2023Article
- Looking at the Pathogenesis of the Rabies Lyssavirus Strain Pasteur Vaccins through a Prism of the Disorder-Based Bioinformatics.Biomolecules · 2022Article
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- New methylene blue derivatives suggest novel anti-orthopoxviral strategies.Antiviral research · 2021Article
- Analysis of the dark proteome of Chandipura virus reveals maximum propensity for intrinsic disorder in phosphoprotein.Scientific reports · 2021Article
- Review
- Identification of an Antiretroviral Small Molecule That Appears To Be a Host-Targeting Inhibitor of HIV-1 Assembly.Journal of virology · 2021Article
- Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2.Frontiers in pharmacology · 2021Article
- Disruption of cellular proteostasis by H1N1 influenza A virus causes α-synuclein aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro.Viruses · 2020Article
- Optimization of Inhibitory Peptides Targeting Phosphoprotein of Rabies Virus.International journal of peptide research and therapeutics · 2020Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
We present an unconventional approach to antiviral drug discovery, which is used to identify potent small molecules against rabies virus. First, we conceptualized viral capsid assembly as occurring via a host-catalyzed biochemical pathway, in contrast to the classical view of capsid formation by self-assembly. This suggested opportunities for antiviral intervention by targeting previously unappreciated catalytic host proteins, which were pursued. Second, we hypothesized these host proteins to be components of heterogeneous, labile, and dynamic multi-subunit assembly machines, not easily isolated by specific target protein-focused methods. This suggested the need to identify active compounds before knowing the precise protein target. A cell-free translation-based small molecule screen was established to recreate the hypothesized interactions involving newly synthesized capsid proteins as host assembly machine substrates. Hits from the screen were validated by efficacy against infectious rabies virus in mammalian cell culture. Used as affinity ligands, advanced analogs were shown to bind a set of proteins that effectively reconstituted drug sensitivity in the cell-free screen and included a small but discrete subfraction of cellular ATP-binding cassette family E1 (ABCE1), a host protein previously found essential for HIV capsid formation. Taken together, these studies advance an alternate view of capsid formation (as a host-catalyzed biochemical pathway), a different paradigm for drug discovery (whole pathway screening without knowledge of the target), and suggest the existence of labile assembly machines that can be rendered accessible as next-generation drug targets by the means described.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.