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@ARTICLE{Chen:278658,
      author       = {Chen, Yuexuan and Klute, Susanne and Sparrer, Konstantin
                      Maria Johannes and Serra-Moreno, Ruth},
      title        = {{RAB}5 is a host dependency factor for the generation of
                      {SARS}-{C}o{V}-2 replication organelles.},
      journal      = {mBio},
      volume       = {16},
      number       = {5},
      issn         = {2161-2129},
      address      = {Washington, DC},
      publisher    = {American Society for Microbiology},
      reportid     = {DZNE-2025-00614},
      pages        = {e0331424},
      year         = {2025},
      abstract     = {Severe acute respiratory syndrome coronavirus 2
                      (SARS-CoV-2) remains a threat due to the emergence of
                      variants with increased transmissibility and enhanced escape
                      from immune responses. Like other coronaviruses before,
                      SARS-CoV-2 likely emerged after its transmission from bats.
                      The successful propagation of SARS-CoV-2 in humans might
                      have been facilitated by usurping evolutionarily conserved
                      cellular factors to execute crucial steps in its life cycle,
                      such as the generation of replication organelles-membrane
                      structures where coronaviruses assemble their
                      replication-transcription complex. In this study, we found
                      that RAB5, which is highly conserved across mammals, is a
                      critical host dependency factor for the replication of the
                      SARS-CoV-2 genome. Our results also suggest that SARS-CoV-2
                      uses RAB5+ membranes to build replication organelles with
                      the aid of COPB1, a component of the COP-I complex, and that
                      the virus protein NSP6 participates in this process. Hence,
                      targeting NSP6 represents a promising approach to interfere
                      with SARS-CoV-2 RNA synthesis and halt its
                      propagation.IMPORTANCEIn this study, we sought to identify
                      the host dependency factors that severe acute respiratory
                      syndrome coronavirus 2 (SARS-CoV-2) uses for the generation
                      of replication organelles: cellular membranous structures
                      that SARS-CoV-2 builds in order to support the replication
                      and transcription of its genome. We uncovered that RAB5 is
                      an important dependency factor for SARS-CoV-2 replication
                      and the generation of replication organelles, and that the
                      viral protein NSP6 participates in this process. Hence, NSP6
                      represents a promising target to halt SARS-CoV-2
                      replication.},
      keywords     = {Humans / rab5 GTP-Binding Proteins: metabolism / rab5
                      GTP-Binding Proteins: genetics / Virus Replication /
                      SARS-CoV-2: physiology / SARS-CoV-2: genetics / Animals /
                      COVID-19: virology / Host-Pathogen Interactions / Vero Cells
                      / Chlorocebus aethiops / Viral Replication Compartments:
                      metabolism / COP-I (Other) / COPB1 (Other) / NSP6 (Other) /
                      RAB5 (Other) / SARS-CoV-2 (Other) / replication organelle
                      (Other) / rab5 GTP-Binding Proteins (NLM Chemicals) / RAB5C
                      protein, human (NLM Chemicals)},
      cin          = {AG Sparrer},
      ddc          = {570},
      cid          = {I:(DE-2719)1910003},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40167317},
      pmc          = {pmc:PMC12077180},
      doi          = {10.1128/mbio.03314-24},
      url          = {https://pub.dzne.de/record/278658},
}