ArticleProceedings of the National Academy of Sciences of the United States of America2022
Proximity interactome analysis of Lassa polymerase reveals eRF3a/GSPT1 as a druggable target for host-directed antivirals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The degradation revolution: harnessing targeted protein degradation for the treatment of human diseases.Cellular and molecular life sciences : CMLS · 2026Review
- Degraders of the dengue virus capsid protein exhibit differentiated pharmacology relative to capsid inhibitors.Nature communications · 2026Article
- CC-90009, a Cereblon E3 Ligase Modulator, Exhibits Antiviral Efficacy Against JEV In Vitro and In Vivo via Targeted Degradation of GSPT1 and Viral NS5 Protein.Pharmaceutics · 2025Article
- Licoisoflavone B and glabridin from Glycyrrhiza glabra as potent nucleoprotein antagonists of Lassa virus: insights from molecular docking, dynamics simulation, PCA, and DFT studies.Journal, genetic engineering & biotechnology · 2025Article
- Proximity interactome of alphavirus replicase component nsP3 includes proviral host factors eIF4G and AHNAK.PLoS pathogens · 2025Article
- DDX3X Promotes Rotavirus Infection and Serves as an Antiviral Target.Transboundary and emerging diseases · 2025Article
- Discovery of Potent Degraders of the Dengue Virus Envelope Protein.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Discovery of Potent Degraders of the Dengue Virus Envelope Protein.bioRxiv : the preprint server for biology · 2024Article
- An integrated approach using proximity labelling and chemical crosslinking to probeQRB discovery · 2024Review
- Interaction of species A rotavirus VP4 with the cellular proteins vimentin and actin related protein 2 discovered by a proximity interactome assay.Journal of virology · 2023Article
- RETICULON-LIKE PROTEIN B2 is a proviral factor co-opted for the biogenesis of viral replication organelles in plants.The Plant cell · 2023Article
- Chemical and Biological Strategies for Profiling Protein-Protein Interactions in Living Cells.Chemistry, an Asian journal · 2023Review
- Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics.Cell host & microbe · 2023Article
- Combating Lassa Fever in West African Sub-Region: Progress, Challenges, and Future Perspectives.Viruses · 2023Review
- The mechanism of genome replication and transcription in bunyaviruses.PLoS pathogens · 2023Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
Completion of the Lassa virus (LASV) life cycle critically depends on the activities of the virally encoded, RNA-dependent RNA polymerase in replication and transcription of the viral RNA genome in the cytoplasm of infected cells. The contribution of cellular proteins to these processes remains unclear. Here, we applied proximity proteomics to define the interactome of LASV polymerase in cells under conditions that recreate LASV RNA synthesis. We engineered a LASV polymerase-biotin ligase (TurboID) fusion protein that retained polymerase activity and successfully biotinylated the proximal proteome, which allowed the identification of 42 high-confidence LASV polymerase interactors. We subsequently performed a small interfering RNA (siRNA) screen to identify those interactors that have functional roles in authentic LASV infection. As proof of principle, we characterized eukaryotic peptide chain release factor subunit 3a (eRF3a/GSPT1), which we found to be a proviral factor that physically associates with LASV polymerase. Targeted degradation of GSPT1 by a small-molecule drug candidate, CC-90009, resulted in strong inhibition of LASV infection in cultured cells. Our work demonstrates the feasibility of using proximity proteomics to illuminate and characterize yet-to-be-defined host-pathogen interactome, which can reveal new biology and uncover novel targets for the development of antivirals against highly pathogenic RNA viruses.
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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.