ArticleScience advances2026
Phospholipid-driven conformational switching of HCV NS5A links protein folding to replication membrane remodeling.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- A novel dimerization site in non-structural protein 5A of hepatitis C virus regulates viral replication fitness.PLoS pathogens · 2026Article
- Phospholipid codes at virus-host membrane interfaces: mechanisms and therapeutic opportunities in animal viral diseases.Frontiers in cellular and infection microbiology · 2026Review
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Phospholipids are essential for RNA virus replication, yet their role in modulating conformational dynamics of membrane-associated viral proteins remains poorly understood. For NS5A, a key replication factor of hepatitis C virus, previous crystallographic models fail to capture the lipid-driven conformational mechanics we uncover here. Using structural informatics and biochemical probing of pharmacophore-guided mutants in defined lipid environments, we evaluated competing NS5A domain 1 dimerization models. Our data reveal an alternative membrane-specific fold stabilized by polyproline hinges and phospholipids (PIPs) such as phosphatidylinositol-4-phosphate, a host lipid enriched at replication membranes. PIP binding promotes a conformational switch that drives dimerization, linking lipid sensing to membrane remodeling and host factor recruitment. This reciprocal mechanism-where a lipid allosterically modulates a viral protein that reshapes membranes-is blocked by the antiviral pibrentasvir. These findings define a lipid-driven structural switch that governs NS5A pleiotropy and highlight dynamic lipid-protein interfaces as targets for antiviral intervention.
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