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AMPs are short peptides active against bacteria, cancer cells, and viruses. It has been shown that the SARS\u2010CoV\u20102 nucleocapsid protein (N\u2212P) undergoes liquid\u2010liquid phase separation in the presence of RNA, resulting in biocondensate formation. These biocondensates are crucial for viral replication as they concentrate the viral RNA with the host cell\u2018s protein machinery required for viral protein expression. Thus, N\u2212P biocondensates are promising targets to block or slow down viral RNA transcription and consequently virion assembly. We investigated the ability of three AMPs to interfere with N\u2212P\/RNA condensates. Using microscopy techniques, supported by biophysical characterization, we found that the AMP LL\u2013III partitions into the condensate, leading to clustering. Instead, the AMP <jats:italic>Cr<\/jats:italic>ACP1 partitions into the droplets without affecting their morphology but reducing their dynamics. Conversely, GKY20 leads to the formation of fibrillar structures after partitioning. It can be expected that such morphological transformation severely impairs the normal functionality of the N\u2212P droplets and thus virion assembly. These results could pave the way for the development of a new class of AMP\u2010based antiviral agents targeting biocondensates.<\/jats:p>","DOI":"10.1002\/chem.202400048","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T12:47:53Z","timestamp":1710420473000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Morphological Transformations of SARS\u2010CoV\u20102 Nucleocapsid Protein Biocondensates Mediated by Antimicrobial Peptides"],"prefix":"10.1002","volume":"30","author":[{"given":"Marco","family":"Campanile","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences University of Naples Federico II  Via Cintia, 26 80126 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emine Dila","family":"Kurtul","sequence":"additional","affiliation":[{"name":"Department Biochemistry of Neurodegenerative Diseases Institute of Biochemistry and Pathobiochemistry Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Dec","sequence":"additional","affiliation":[{"name":"Physical Chemistry I \u2013 Biophysical Chemistry Department of Chemistry and Chemical Biology TU Dortmund University  Otto-Hahn-Strasse 4a 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"M\u00f6bitz","sequence":"additional","affiliation":[{"name":"Physical Chemistry I \u2013 Biophysical Chemistry Department of Chemistry and Chemical Biology TU Dortmund University  Otto-Hahn-Strasse 4a 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-3478","authenticated-orcid":false,"given":"Pompea","family":"Del Vecchio","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences University of Naples Federico II  Via Cintia, 26 80126 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-2897","authenticated-orcid":false,"given":"Luigi","family":"Petraccone","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences University of Naples Federico II  Via Cintia, 26 80126 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5017-5528","authenticated-orcid":false,"given":"J\u00f6rg","family":"Tatzelt","sequence":"additional","affiliation":[{"name":"Department Biochemistry of Neurodegenerative Diseases Institute of Biochemistry and Pathobiochemistry Ruhr University Bochum  44801 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-1768","authenticated-orcid":false,"given":"Rosario","family":"Oliva","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences University of Naples Federico II  Via Cintia, 26 80126 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-6928","authenticated-orcid":false,"given":"Roland","family":"Winter","sequence":"additional","affiliation":[{"name":"Physical Chemistry I \u2013 Biophysical Chemistry Department of Chemistry and Chemical Biology TU Dortmund University  Otto-Hahn-Strasse 4a 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,10]]},"reference":[{"key":"e_1_2_3_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3303"},{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/v6082991"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19843-1"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00408-2"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13061115"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2022.103353"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2011.12.005"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.01.003"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15010072"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-022-00432-6"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0240004"},{"key":"e_1_2_3_13_1","doi-asserted-by":"crossref","unstructured":"W.\u2005T. 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