ArticleNature medicine2012
Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 231 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.
A Pilot Study of the Effect of Ezetimibe in Patients With Chronic Hepatitis C Infection
Pilot Study of Ezetimibe for Chronic Hepatitis C Virus (HCV) Infection in Liver Transplant Candidates (EZE-2)
Who cites it
231 citing papers in PubMed, 435 citations in OpenAlex.
- Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study.The lancet. Gastroenterology & hepatology · 2020Trial
- A randomized, proof-of-concept clinical trial on repurposing chlorcyclizine for the treatment of chronic hepatitis C.Antiviral research · 2019Trial
- Outcomes After 4-Week Course of Sofosbuvir/Velpatasvir Therapy in Hepatitis C Seronegative Recipients of Kidneys From Hepatitis C Viremic Deceased Donors.Clinical transplantation · 2026Article
- Pathogenesis, prevention, and therapeutic advances in hepatitis B, C, and D.Virology journal · 2025Review
- Functional Role of Hepatitis C Virus NS5A in the Regulation of Autophagy.Pathogens (Basel, Switzerland) · 2024Review
- NPC1L1 rs217434 A > G as a Novel Single Nucleotide Polymorphism Related to Dyslipidemia in a Korean Population.Biochemical genetics · 2024Article
- Targeting NTCP for liver disease treatment: A promising strategy.Journal of pharmaceutical analysis · 2024Review
- Co-Expression of Niemann-Pick Type C1-Like1 (NPC1L1) with ACE2 Receptor Synergistically Enhances SARS-CoV-2 Entry and Fusion.Biomedicines · 2024Article
- GB Virus B and Hepatitis C Virus, Distantly Related Hepaciviruses, Share an Entry Factor, Claudin-1.Journal of virology · 2023Article
- Cholesterol-Lowering Drugs as Potential Antivirals: A Repurposing Approach against Flavivirus Infections.Viruses · 2023Article
- Natural flavonoids effectively block the CD81 receptor of hepatocytes and inhibit HCV infection: a computational drug development approach.Molecular diversity · 2023Article
- Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact.Biomedicines · 2023Review
- The Role of Cytosolic Lipid Droplets in Hepatitis C Virus Replication, Assembly, and Release.BioMed research international · 2023Review
- A single mutation in the E2 glycoprotein of hepatitis C virus broadens the claudin specificity for its infection.Scientific reports · 2022Article
- Hepatitis D virus (HDV): investigational therapeutic agents in clinical trials.Expert opinion on investigational drugs · 2022Review
- The NPC Families Mediate BmNPV Entry.Microbiology spectrum · 2022Article
- Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds.International journal of molecular sciences · 2022Review
- Apolipoprotein E, a Crucial Cellular Protein in the Lifecycle of Hepatitis Viruses.International journal of molecular sciences · 2022Review
- Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization.Immunity · 2022Article
- Entry Inhibitors of Hepatitis C Virus.Advances in experimental medicine and biology · 2022Article
171 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. With ∼170 million individuals infected and current interferon-based treatment having toxic side effects and marginal efficacy, more effective antivirals are crucially needed. Although HCV protease inhibitors were just approved by the US Food and Drug Administration (FDA), optimal HCV therapy, analogous to HIV therapy, will probably require a combination of antivirals targeting multiple aspects of the viral lifecycle. Viral entry represents a potential multifaceted target for antiviral intervention; however, to date, FDA-approved inhibitors of HCV cell entry are unavailable. Here we show that the cellular Niemann-Pick C1-like 1 (NPC1L1) cholesterol uptake receptor is an HCV entry factor amendable to therapeutic intervention. Specifically, NPC1L1 expression is necessary for HCV infection, as silencing or antibody-mediated blocking of NPC1L1 impairs cell culture-derived HCV (HCVcc) infection initiation. In addition, the clinically available FDA-approved NPC1L1 antagonist ezetimibe potently blocks HCV uptake in vitro via a virion cholesterol-dependent step before virion-cell membrane fusion. Moreover, ezetimibe inhibits infection by all major HCV genotypes in vitro and in vivo delays the establishment of HCV genotype 1b infection in mice with human liver grafts. Thus, we have not only identified NPC1L1 as an HCV cell entry factor but also discovered a new antiviral target and potential therapeutic agent.
Indexed as
Identifiers
What OpenQuestion holds
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.