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@ARTICLE{SchamoniKast:637344,
      author       = {Schamoni-Kast, Kira and Uetrecht, Charlotte},
      title        = {{F}rom {S}cience to {F}iction – {C}onnecting {I}n {V}ivo
                      and {I}n {V}itro {R}esults in {P}olyprotein {P}rocessing of
                      {C}oronaviruses},
      journal      = {Journal of molecular biology},
      volume       = {437},
      number       = {22},
      issn         = {0022-2836},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {PUBDB-2025-03836},
      pages        = {169370},
      year         = {2025},
      abstract     = {Polyprotein processing is a common strategy in many
                      positive sense single-stranded RNA ((+)ssRNA) viruses. This
                      highly regulated process is crucial for viral progeny and
                      ensures the release of functional replicase proteins in the
                      correct location and at the right time. Coronaviruses (CoVs)
                      have one of the largest genomes on average among (+)ssRNA
                      viruses requiring a unique replication-transcription complex
                      (RTC) with proofreading function that prevents error
                      catastrophe. Two thirds of the CoV genome encode for the
                      non-structural proteins (nsps) that drive replication. These
                      are directly synthesized by RNA genome translation after
                      infection as two large polyproteins pp1a and pp1ab. A
                      regulated polyprotein proteolytic auto-processing is
                      essential for viral growth and always has been an
                      interesting target for therapeutics.Here, we present an
                      overview of polyprotein processing and RTC research in CoVs
                      in vitro and in vivo over the last 30 years. We highlight
                      cutting-edge methodologies such as super resolution
                      microscopy or structural mass spectrometry approaches and
                      demonstrate how these have contributed to polyprotein
                      research, e.g. by providing comprehensive structural models.
                      We illustrate exciting examples of polyprotein processing in
                      other viruses that could be transferred to CoVs, too.
                      Additionally, we identify critical knowledge gaps in
                      polyprotein processing and RTC assembly, proposing future
                      perspectives to address these limitations.},
      cin          = {CSSB-LIV/DESY-CU},
      ddc          = {610},
      cid          = {$I:(DE-H253)CSSB-LIV_DESY-CU-20220525$},
      pnm          = {633 - Life Sciences – Building Blocks of Life: Structure
                      and Function (POF4-633) / ARIADNE - Redefining mass
                      spectrometry – a breakthrough platform for real-time
                      noninvasive breath analysis with single ion detection of
                      intact viruses and bacteria and post-analysis molecular
                      characterization (964553) / SPOCkS MS - Sampling Protein
                      cOmplex Conformational Space with native top down Mass
                      Spectrometry (759661)},
      pid          = {G:(DE-HGF)POF4-633 / G:(EU-Grant)964553 /
                      G:(EU-Grant)759661},
      experiment   = {EXP:(DE-MLZ)NOSPEC-20140101},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1016/j.jmb.2025.169370},
      url          = {https://bib-pubdb1.desy.de/record/637344},
}