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@ARTICLE{Weil:284347,
      author       = {Weil, Tatjana and Lawrenz, Jan and Taghuo Kaptouom, Estelle
                      and Mieres-Perez, Joel and Hunszinger, Victoria and Sparrer,
                      Konstantin M J and Almeida-Hernandez, Yasser and Schrader,
                      Thomas and Sanchez-Garcia, Elsa and Münch, Jan},
      title        = {{A}dvanced {M}olecular {T}weezers {E}ffectively {T}arget
                      {M}embranes {L}acking {C}holine {H}eadgroups for
                      {B}road-{S}pectrum {A}ntiviral {E}fficacy.},
      journal      = {Journal of the American Chemical Society},
      volume       = {148},
      number       = {3},
      issn         = {0002-7863},
      address      = {Washington, DC},
      publisher    = {ACS Publications},
      reportid     = {DZNE-2026-00118},
      pages        = {3626 - 3637},
      year         = {2026},
      abstract     = {Broad-spectrum antivirals are urgently required to counter
                      present and emerging viral threats. It has previously been
                      shown that the parental molecular tweezers CLR01 and CLR05
                      disrupt viral envelopes by complexing choline headgroups and
                      that ester-functionalized 'advanced' tweezers display
                      markedly enhanced antiviral potency. Here, we determine the
                      molecular basis of this improved activity. Using liposome
                      leakage assays, giant unilamellar vesicles, NMR, Langmuir
                      film balance experiments, and atomistic simulations, we
                      demonstrate that advanced tweezers not only encapsulate
                      choline-containing lipids but also engage lipids lacking
                      choline headgroups via transient and conserved hydrophobic
                      insertion events. These interactions preferentially
                      destabilize membranes enriched in sphingomyelin, unsaturated
                      acyl chains, or inverted cone-shaped lipids and are
                      especially effective against small, highly curved particles
                      resembling viral particles, explaining their broad antiviral
                      activity for enveloped viruses. Our findings reveal a dual
                      mechanism of action, choline binding and hydrophobic
                      insertion, that underpins the broad-spectrum antiviral
                      activity of advanced molecular tweezers and establish them
                      as a promising new class of membrane-targeting antivirals
                      for prophylactic and therapeutic use.},
      cin          = {AG Sparrer},
      ddc          = {540},
      cid          = {I:(DE-2719)1910003},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41552975},
      doi          = {10.1021/jacs.5c19450},
      url          = {https://pub.dzne.de/record/284347},
}