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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
09:10

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Conserved requirement of autophagy-related effectors during coronavirus replication

Yannick Brüggemann1, Annika Kratzel2,3,4, Lea Almeida2,3,4

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

Autophagy
|July 25, 2022
PubMed

Insights

Novel treatments are needed for emerging coronaviruses (CoVs). Researchers identified autophagy-related proteins FKBP8, TMEM41B, and MINAR1 as key host factors for multiple CoVs, including SARS-CoV-2, offering potential therapeutic targets.

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • Zoonotic transmission of coronaviruses (CoVs) like SARS-CoV, MERS-CoV, and SARS-CoV-2 necessitates new therapeutic strategies.
  • Understanding host dependency factors (HDFs) is crucial for developing broad-spectrum antiviral treatments.

Purpose of the Study:

  • To identify conserved and specific host factors essential for the life cycle of various CoVs using a genome-wide CRISPR knockout screen.
  • To investigate the role of autophagy pathway-regulating immunophilins as potential therapeutic targets against emerging CoVs.

Main Methods:

  • Genome-wide CRISPR knockout screening was employed to identify essential host genes for CoV replication.
  • Comparative analysis was performed to distinguish pan-coronavirus HDFs from those specific to MERS-CoV or HCoV-229E.
  • The identified host factors were further analyzed for their role in the life cycle of SARS-CoV and SARS-CoV-2.

Main Results:

  • A list of conserved pan-coronavirus HDFs and CoV-specific HDFs was generated.
  • FKBP8, TMEM41B, and MINAR1 were identified as conserved host factors essential for MERS-CoV, HCoV-229E, SARS-CoV, and SARS-CoV-2.
  • These identified factors are regulators of the macroautophagy/autophagy pathway.

Conclusions:

  • Autophagy pathway-regulating immunophilins FKBP8, TMEM41B, and MINAR1 are critical host factors for a range of coronaviruses.
  • These host factors represent promising targets for therapeutic intervention against emerging and re-emerging CoV infections.
  • Clinically approved drugs targeting these pathways could be repurposed for novel antiviral therapies.
Keywords:
Antiviral targetCRISPR screenautophagycoronavirushost factor

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