ArticleGastroenterology2015
Alisporivir inhibition of hepatocyte cyclophilins reduces HBV replication and hepatitis B surface antigen production.
Article in Gastroenterology, 2015. 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, 57 citations in OpenAlex.
- Review
- Human Cyclophilins-An Emerging Class of Drug Targets.Medicinal research reviews · 2026Review
- Hepatitis B virus rtCYE/rtCYEI mutations may contribute limited tenofovir resistance: Analysis of a large sample of Chinese patients.World journal of hepatology · 2025Article
- CypA inhibits respiratory syncytial virus (RSV) replication by suppressing glycolysis through the downregulation of PKM2 expression.Journal of virology · 2025Article
- Article
- Cyclophilin inhibition as a strategy for the treatment of human disease.Frontiers in pharmacology · 2024Review
- Cyclophilin A facilitates influenza B virus replication by stabilizing viral proteins.iScience · 2023Article
- Review
- Cell Culture Systems for Studying Hepatitis B and Hepatitis D Virus Infections.Life (Basel, Switzerland) · 2023Review
- Article
- Review
- Novel therapeutic strategies for chronic hepatitis B.Virulence · 2022Review
- Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents.Drug discovery today · 2022Review
- Review
- Current update on theranostic roles of cyclophilin A in kidney diseases.Theranostics · 2022Review
- From hepatitis A to E: A critical review of viral hepatitis.World journal of gastroenterology · 2021Review
- Cyclophilin A: a key player for etiological agent infection.Applied microbiology and biotechnology · 2021Review
- Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.Frontiers in pharmacology · 2021Review
- The Hepatitis B Virus Interactome: A Comprehensive Overview.Frontiers in microbiology · 2021Review
- Investigational drugs with dual activity against HBV and HIV (Review).Experimental and therapeutic medicine · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsCyclophilins are host factors required for hepatitis C virus replication. Cyclophilin inhibitors such as alisporivir have shown strong anti-hepatitis C virus activity in vitro and in clinical studies. However, little is known about whether hepatocyte cyclophilins are involved in the hepatitis B virus (HBV) life cycle. We investigated the effects of 2 cyclophilin inhibitors (alisporivir and NIM811) on HBV replication and hepatitis B surface antigen (HBsAg) production in cell lines.
methodsLiver-derived cell lines producing full-length HBV and HBsAg particles, owing to stable (HepG2215) or transient (HuH-7) transfection, or infected with HBV (HepaRG cells; Invitrogen [Carlsbad, CA]), were incubated with alisporivir or NIM811 alone, or alisporivir in combination with a direct antiviral (telbivudine). The roles of individual cyclophilins in drug response was evaluated by small interfering RNA knockdown of cyclophilin (CYP)A, CYPC, or CYPD in HepG2215 cells, or CYPA knockdown in HuH-7 cells. The kinetics of antiviral activity were assessed based on levels of HBV DNA and HBsAg and Southern blot analysis.
resultsIn HepG2215, HuH-7, and HepaRG cells, alisporivir reduced intracellular and secreted HBV DNA, in a dose-dependent manner. Knockdown of CYPA, CYPC, or CYPD (reduced by 80%) significantly reduced levels of HBV DNA and secreted HBsAg. Knockdown of CYPA significantly reduced secretion of HBsAg, leading to accumulation of intracellular HBsAg; the addition of alisporivir greatly reduced levels of HBsAg in these cells. The combination of alisporivir and telbivudine had greater antiviral effects than those of telbivudine or alisporivir alone.
conclusionsAlisporivir inhibition of cyclophilins in hepatocyte cell lines reduces replication of HBV DNA and HBsAg production and secretion. These effects are potentiated in combination with direct antiviral agents that target HBV-DNA polymerase.
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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.