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@ARTICLE{Eberle:904310,
      author       = {Eberle, Raphael J. and Olivier, Danilo S. and Pacca,
                      Carolina C. and Avilla, Clarita M. S. and Nogueira, Mauricio
                      L. and Amaral, Marcos S. and Willbold, Dieter and Arni,
                      Raghuvir K. and Coronado, Monika A.},
      title        = {{I}n vitro study of {H}esperetin and {H}esperidin as
                      inhibitors of zika and chikungunya virus proteases},
      journal      = {PLOS ONE},
      volume       = {16},
      number       = {3},
      issn         = {1932-6203},
      address      = {San Francisco, California, US},
      publisher    = {PLOS},
      reportid     = {FZJ-2021-05880},
      pages        = {e0246319 -},
      year         = {2021},
      abstract     = {The potential outcome of flavivirus and alphavirus
                      co-infections is worrisome due to the development of severe
                      diseases. Hundreds of millions of people worldwide live
                      under the risk of infections caused by viruses like
                      chikungunya virus (CHIKV, genus Alphavirus), dengue virus
                      (DENV, genus Flavivirus), and zika virus (ZIKV, genus
                      Flavivirus). So far, neither any drug exists against the
                      infection by a single virus, nor against co-infection. The
                      results described in our study demonstrate the inhibitory
                      potential of two flavonoids derived from citrus plants:
                      Hesperetin (HST) against NS2B/NS3pro of ZIKV and nsP2pro of
                      CHIKV and, Hesperidin (HSD) against nsP2pro of CHIKV. The
                      flavonoids are noncompetitive inhibitors and the determined
                      IC50 values are in low µM range for HST against ZIKV
                      NS2B/NS3pro (12.6 ± 1.3 µM) and against CHIKV nsP2pro (2.5
                      ± 0.4 µM). The IC50 for HSD against CHIKV nsP2pro was 7.1
                      ± 1.1 µM. The calculated ligand efficiencies for HST were
                      > 0.3, which reflect its potential to be used as a lead
                      compound. Docking and molecular dynamics simulations display
                      the effect of HST and HSD on the protease 3D models of CHIKV
                      and ZIKV. Conformational changes after ligand binding and
                      their effect on the substrate-binding pocket of the
                      proteases were investigated. Additionally, MTT assays
                      demonstrated a very low cytotoxicity of both the molecules.
                      Based on our results, we assume that HST comprise a chemical
                      structure that serves as a starting point molecule to
                      develop a potent inhibitor to combat CHIKV and ZIKV
                      co-infections by inhibiting the virus proteases.},
      cin          = {IBI-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5244},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33661906},
      UT           = {WOS:000626604100104},
      doi          = {10.1371/journal.pone.0246319},
      url          = {https://juser.fz-juelich.de/record/904310},
}