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@ARTICLE{Chatziefthymiou:631520,
      author       = {Chatziefthymiou, Spyros D. and Kuzikov, Maria and Afandi,
                      Sara and Kovacs, Greta and Srivastava, Sukrit and Zaliani,
                      Andrea and Gruzinov, Andrey and Pompidor, Guillaume and
                      Lunelli, Michele and Ahmed, Golam Rizvee and Labahn, Jörg
                      and Hakanpää, Johanna and Windshügel, Björn and Kolbe,
                      Michael},
      title        = {{I}dentification, validation, and characterization of
                      approved and investigational drugs interfering with the
                      {SARS} ‐ {C}o{V} ‐2 endoribonuclease {N}sp15},
      journal      = {Protein science},
      volume       = {34},
      number       = {6},
      issn         = {0961-8368},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {PUBDB-2025-02032},
      pages        = {e70156},
      year         = {2025},
      note         = {This research was funded by the DESY Strategic Fund (DSF)
                      and by the Horizon Europe Framework Programme (grant
                      agreement number 101137192, AVI-THRAPID).},
      abstract     = {Since the emergence of SARS-CoV-2 at the end of 2019, the
                      virus has caused significant global health and economic
                      disruptions. Despite the rapid development of antiviral
                      vaccines and some approved treatments such as remdesivir and
                      paxlovid, effective antiviral pharmacological treatments for
                      COVID-19 patients remain limited. This study explores Nsp15,
                      a 3′-uridylate-specific RNA endonuclease, which has a
                      critical role in immune system evasion and hence in escaping
                      the innate immune sensors. We conducted a comprehensive drug
                      repurposing screen and identified 44 compounds that showed
                      more than $55\%$ inhibition of Nsp15 activity in a real-time
                      fluorescence assay. A validation pipeline was employed to
                      exclude unspecific interactions, and dose–response assays
                      confirmed 29 compounds with an IC$_{50}$ below 10 μM.
                      Structural studies, including molecular docking and x-ray
                      crystallography, revealed key interactions of identified
                      inhibitors, such as TAS-103 and YM-155, with the Nsp15
                      active site and other critical regions. Our findings show
                      that the identified compounds, particularly those retaining
                      potency under different assay conditions, could serve as
                      promising hits for developing Nsp15 inhibitors.
                      Additionally, the study emphasizes the potential of
                      combination therapies targeting multiple viral processes to
                      enhance treatment efficacy and reduce the risk of drug
                      resistance. This research contributes to the ongoing efforts
                      to develop effective antiviral therapies for SARS-CoV-2 and
                      possibly other coronaviruses.},
      cin          = {CSSB-HZI-MK / CSSB-CF-SPC},
      ddc          = {610},
      cid          = {I:(DE-H253)CSSB-HZI-MK-20210520 /
                      I:(DE-H253)CSSB-CF-SPC-20210520},
      pnm          = {633 - Life Sciences – Building Blocks of Life: Structure
                      and Function (POF4-633)},
      pid          = {G:(DE-HGF)POF4-633},
      experiment   = {EXP:(DE-H253)P-P11-20150101 / EXP:(DE-H253)P-P12-20150101},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1002/pro.70156},
      url          = {https://bib-pubdb1.desy.de/record/631520},
}