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The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors

Susanne Pfefferle1, Julia Schöpf, Manfred Kögl

  • 1Bernhard-Nocht-Institute, Hamburg, Germany.

Plos Pathogens
|November 3, 2011
PubMed

Insights

Scientists identified immunophilins as key targets for fighting coronaviruses (CoVs). Inhibiting these proteins with cyclosporine A blocked CoV replication, offering a potential broad-spectrum antiviral strategy against emerging and existing CoV threats.

Area of Science:

  • Virology
  • Immunology
  • Systems Biology

Background:

  • Coronaviruses (CoVs) are significant human and animal pathogens causing severe diseases.
  • The lack of available vaccines and therapeutics against CoVs highlights the need for novel antiviral strategies.
  • Understanding virus-host interactions is crucial for identifying broad-spectrum antiviral targets.

Purpose of the Study:

  • To identify host cell proteins interacting with CoV non-structural protein 1 (Nsp1) using a systems biology approach.
  • To investigate the role of identified interaction partners in CoV replication and pathogenesis.
  • To evaluate the potential of targeting these interactions for broad-spectrum antiviral therapy.

Main Methods:

  • Genome-wide yeast-two hybrid interaction screening to identify CoV Nsp1 binding partners.
  • Analysis of the Calcineurin/NFAT pathway modulation by identified host factors.
  • Infection studies with various CoV genera to assess the antiviral efficacy of cyclosporine A (CspA).

Main Results:

  • Immunophilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) were identified as Nsp1 interaction partners.
  • Nsp1 and SARS-CoV infection enhanced Calcineurin/NFAT pathway signaling and interleukin 2 induction.
  • Cyclosporine A (CspA) effectively blocked the replication of multiple CoV genera, including SARS-CoV, HCoV-229E, HCoV-NL-63, Feline CoV, and Avian IBV.

Conclusions:

  • Immunophilins are critical host factors involved in CoV replication and pathogenesis.
  • Inhibition of cyclophilins by CspA demonstrates broad-spectrum antiviral activity against diverse CoVs.
  • Non-immunosuppressive CspA derivatives represent promising candidates for broad-range CoV inhibitors against emerging and existing threats.

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