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@ARTICLE{Costanzi:902158,
      author       = {Costanzi, Elisa and Kuzikov, Maria and Esposito, Francesca
                      and Albani, Simone and Demitri, Nicola and Giabbai, Barbara
                      and Camasta, Marianna and Tramontano, Enzo and Rossetti,
                      Giulia and Zaliani, Andrea and Storici, Paola},
      title        = {{S}tructural and {B}iochemical {A}nalysis of the {D}ual
                      {I}nhibition of {MG}-132 against {SARS}-{C}o{V}-2 {M}ain
                      {P}rotease ({M}pro/3{CL}pro) and {H}uman {C}athepsin-{L}},
      journal      = {International journal of molecular sciences},
      volume       = {22},
      number       = {21},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {FZJ-2021-04067},
      pages        = {11779 -},
      year         = {2021},
      abstract     = {After almost two years from its first evidence, the
                      COVID-19 pandemic continues to afflict people worldwide,
                      highlighting the need for multiple antiviral strategies.
                      SARS-CoV-2 main protease (Mpro/3CLpro) is a recognized
                      promising target for the development of effective drugs.
                      Because single target inhibition might not be sufficient to
                      block SARS-CoV-2 infection and replication, multi
                      enzymatic-based therapies may provide a better strategy.
                      Here we present a structural and biochemical
                      characterization of the binding mode of MG-132 to both the
                      main protease of SARS-CoV-2, and to the human Cathepsin-L,
                      suggesting thus an interesting scaffold for the development
                      of double-inhibitors. X-ray diffraction data show that
                      MG-132 well fits into the Mpro active site, forming a
                      covalent bond with Cys145 independently from reducing agents
                      and crystallization conditions. Docking of MG-132 into
                      Cathepsin-L well-matches with a covalent binding to the
                      catalytic cysteine. Accordingly, MG-132 inhibits Cathepsin-L
                      with nanomolar potency and reversibly inhibits Mpro with
                      micromolar potency, but with a prolonged residency time. We
                      compared the apo and MG-132-inhibited structures of Mpro
                      solved in different space groups and we identified a new apo
                      structure that features several similarities with the
                      inhibited ones, offering interesting perspectives for future
                      drug design and in silico efforts.},
      cin          = {IAS-5 / JSC / INM-9},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)JSC-20090406 /
                      I:(DE-Juel1)INM-9-20140121},
      pnm          = {5252 - Brain Dysfunction and Plasticity (POF4-525) / 5111 -
                      Domain-Specific Simulation $\&$ Data Life Cycle Labs (SDLs)
                      and Research Groups (POF4-511)},
      pid          = {G:(DE-HGF)POF4-5252 / G:(DE-HGF)POF4-5111},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {34769210},
      UT           = {WOS:000721074900001},
      doi          = {10.3390/ijms222111779},
      url          = {https://juser.fz-juelich.de/record/902158},
}