ArticlePLoS neglected tropical diseases2016
Selective Inhibitor of Nuclear Export (SINE) Compounds Alter New World Alphavirus Capsid Localization and Reduce Viral Replication in Mammalian Cells.
Article in PLoS neglected tropical diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- Importin α1 contributes to Venezuelan equine encephalitis virus-induced cell death, but is not required for the capsid-mediated blockage of nucleocytoplasmic trafficking.Frontiers in microbiology · 2026Article
- Use of the Split Luciferase Complementation Assay to Identify Novel Small Molecules That Disrupt Essential Protein-Protein Interactions of Viruses.Biomolecules · 2025Article
- The sticky business of Alphavirus capsid-host interactions.Trends in microbiology · 2025Review
- Can Free Energy Perturbation Simulations Coupled with Replica-Exchange Molecular Dynamics Study Ligands with Distributed Binding Sites?Journal of chemical information and modeling · 2023Article
- Binding of Venezuelan Equine Encephalitis Virus Inhibitors to Importin-α Receptors Explored with All-Atom Replica Exchange Molecular Dynamics.The journal of physical chemistry. B · 2023Article
- Article
- EGR1 Upregulation during Encephalitic Viral Infections Contributes to Inflammation and Cell Death.Viruses · 2022Article
- Article
- T helper type (Th1/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: From cytokines produced to immune responses.Transplant immunology · 2022Review
- Anti-Osteoclast Effect of Exportin-1 Inhibitor Eltanexor on Osteoporosis Depends on Nuclear Accumulation of IκBα-NF-κB p65 Complex.Frontiers in pharmacology · 2022Article
- Reversible disruption of XPO1-mediated nuclear export inhibits respiratory syncytial virus (RSV) replication.Scientific reports · 2021Article
- Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection.The Journal of biological chemistry · 2021Review
- Proteomic Discovery of VEEV E2-Host Partner Interactions Identifies GRP78 Inhibitor HA15 as a Potential Therapeutic for Alphavirus Infections.Pathogens (Basel, Switzerland) · 2021Article
- Resveratrol Inhibits Venezuelan Equine Encephalitis Virus Infection by Interfering with the AKT/GSK Pathway.Plants (Basel, Switzerland) · 2021Article
- Targeting XPO1 enhances innate immune response and inhibits KSHV lytic replication during primary infection by nuclear stabilization of the p62 autophagy adaptor protein.Cell death & disease · 2021Article
- Application ofFrontiers in chemistry · 2020Review
- Review
- Novel RU486 (mifepristone) analogues with increased activity against Venezuelan Equine Encephalitis Virus but reduced progesterone receptor antagonistic activity.Scientific reports · 2019Article
- Verdinexor (KPT-335), a Selective Inhibitor of Nuclear Export, Reduces Respiratory Syncytial Virus ReplicationJournal of virology · 2019Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible. Chemically inhibiting CRM1 with these compounds enhanced capsid localization to the nucleus compared to the inactive compound KPT-301, as indicated by immunofluorescent confocal microscopy. Differences in extracellular versus intracellular viral RNA, as well as decreased capsid in cell free supernatants, indicated the inhibitors affected viral assembly, which led to a decrease in viral titers. The decrease in viral replication was confirmed using a luciferase-tagged virus and through plaque assays. SINE compounds had no effect on VEEV TC83_Cm, which encodes a mutated form of capsid that is unable to enter the nucleus. Serially passaging VEEV in the presence of KPT-185 resulted in mutations within the nuclear localization and nuclear export signals of capsid. Finally, SINE compound treatment also reduced the viral titers of the related eastern and western equine encephalitis viruses, suggesting that CRM1 maintains a common interaction with capsid proteins across the New World alphavirus genus.
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