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Related Concept Videos

Hepatitis01:25

Hepatitis

Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Antiviral Nucleoside Inhibitors01:22

Antiviral Nucleoside Inhibitors

Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
Viral Hepatitis I: Introduction01:28

Viral Hepatitis I: Introduction

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Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...

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Related Experiment Video

Updated: Jun 12, 2026

Surface Functionalization of Hepatitis E Virus Nanoparticles Using Chemical Conjugation Methods
09:12

Surface Functionalization of Hepatitis E Virus Nanoparticles Using Chemical Conjugation Methods

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Targeting cellular cathepsins inhibits hepatitis E virus entry.

Mara Klöhn1, Thomas Burkard1, Juliana Janzen1

  • 1Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.

Hepatology (Baltimore, Md.)
|May 10, 2024
PubMed
Summary

Blocking lysosomal cathepsins, particularly Cathepsin L (CTSL), effectively inhibits Hepatitis E virus (HEV) entry. The pan-cathepsin inhibitor K11777 shows significant anti-HEV potential with a good safety profile.

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Area of Science:

  • Hepatology
  • Virology
  • Drug Discovery

Background:

  • Hepatitis E virus (HEV) causes significant mortality, yet effective therapies are limited.
  • Targeting viral entry is a promising strategy for antiviral development.
  • Host factors, including cellular proteases, are crucial for viral entry but remain poorly understood for HEV.

Purpose of the Study:

  • To investigate the role of cellular proteases in HEV entry.
  • To evaluate the therapeutic potential of targeting cellular proteases for HEV infection.

Main Methods:

  • Utilized an established HEV cell culture model and subgenomic HEV replicons.
  • Employed small molecule inhibitors to block lysosomal cathepsins.
  • Conducted time-of-addition and RNAscope experiments.
  • Generated Cathepsin L (CTSL) knockout cells.
  • Analyzed cleavage of HEV ORF2 protein by recombinant CTSL.

Main Results:

  • Inhibition of lysosomal cathepsins (CTS) blocked HEV infection without affecting viral replication.
  • The pan-cathepsin inhibitor K11777 demonstrated potent anti-HEV activity (EC50 ~0.02 nM) with low toxicity in hepatoma cells, HepaRG, and primary human hepatocytes.
  • Cathepsin L (CTSL) was identified as critical for HEV infection, with CTSL knockout cells showing reduced permissiveness.
  • HEV entry was confirmed to be blocked by cathepsin inhibition.
  • Recombinant CTSL cleaved the glycosylated HEV ORF2 protein and HEV particles.

Conclusions:

  • Lysosomal cathepsins, especially CTSL, play a critical role in the HEV entry process.
  • The pan-cathepsin inhibitor K11777 exhibits significant anti-HEV efficacy and a favorable safety profile in primary cells, indicating its therapeutic potential.