Universität zu Köln

Roth, Annika ORCID: 0000-0002-3376-0968, Lütke, Steffen ORCID: 0000-0001-6924-7990, Mörgelin, Matthias, Meinberger, Denise ORCID: 0000-0002-7786-6000, Hermes, Gabriele, Sengle, Gerhard ORCID: 0000-0003-3932-1242, Koch, Manuel ORCID: 0000-0002-2962-7814, Drexelius, Marco ORCID: 0000-0002-5813-2116, Gebauer, Jan ORCID: 0000-0002-3989-4748, Neundorf, Ines ORCID: 0000-0001-6450-3991, Elezagic, Dzemal ORCID: 0000-0003-1041-8470, Paulsson, Mats ORCID: 0000-0002-6846-857X, Streichert, Thomas ORCID: 0000-0002-6588-720X and Klatt, Andreas R. ORCID: 0000-0002-8517-7512 (2025). Vitamin D-inducible antimicrobial peptide LL-37 binds SARS-CoV-2 Spike and accessory proteins ORF7a and ORF8. Frontiers in Cellular and Infection Microbiology, 15. Frontiers. ISSN 2235-2988

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Abstract

[Artikel-Nr. 1671738] Background: The role of vitamin D in Coronavirus Disease 2019 (COVID-19) outcomes remains debated, but emerging evidence suggests it may enhance recovery by strengthening immune responses. Vitamin D upregulates LL-37, an antimicrobial peptide with broad antiviral activity, including potential benefits against SARS-CoV-2. LL-37’s interactions with viral proteins, however, remain incompletely understood. Methods: We investigated LL-37’s interactions with the SARS-CoV-2 Spike glycoprotein and the accessory proteins ORF7a and ORF8 using surface plasmon resonance and negative-stain electron microscopy. These approaches were employed to assess LL-37’s binding capabilities and potential impact on viral infectivity. Results: LL-37 bound multiple domains of the Spike protein and inhibited its interaction with the human angiotensin-converting enzyme 2 (hACE2) receptor in vitro . Up to seven LL-37 molecules were observed surrounding Spike, forming a halo-like structure that may block receptor engagement. LL-37 also bound to ORF7a and ORF8, potentially impairing their ability to disrupt host cell processes. Notably, LL-37’s interaction with ORF7a may prevent degradation of SNAP29, restoring autophagy and promoting viral clearance. Conclusions: LL-37 disrupts key viral-host interactions by binding to Spike, ORF7a, and ORF8, thereby reducing SARS-CoV-2 infectivity. These findings highlight LL-37’s potential as a therapeutic agent in COVID-19 and provide mechanistic insight into its antiviral actions.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Roth, Annika UNSPECIFIED https://orcid.org/0000-0002-3376-0968 UNSPECIFIED Lütke, Steffen UNSPECIFIED https://orcid.org/0000-0001-6924-7990 UNSPECIFIED Mörgelin, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Meinberger, Denise UNSPECIFIED https://orcid.org/0000-0002-7786-6000 UNSPECIFIED Hermes, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Sengle, Gerhard UNSPECIFIED https://orcid.org/0000-0003-3932-1242 UNSPECIFIED Koch, Manuel UNSPECIFIED https://orcid.org/0000-0002-2962-7814 UNSPECIFIED Drexelius, Marco UNSPECIFIED https://orcid.org/0000-0002-5813-2116 UNSPECIFIED Gebauer, Jan UNSPECIFIED https://orcid.org/0000-0002-3989-4748 UNSPECIFIED Neundorf, Ines UNSPECIFIED https://orcid.org/0000-0001-6450-3991 UNSPECIFIED Elezagic, Dzemal UNSPECIFIED https://orcid.org/0000-0003-1041-8470 UNSPECIFIED Paulsson, Mats UNSPECIFIED https://orcid.org/0000-0002-6846-857X UNSPECIFIED Streichert, Thomas UNSPECIFIED https://orcid.org/0000-0002-6588-720X UNSPECIFIED Klatt, Andreas R. UNSPECIFIED https://orcid.org/0000-0002-8517-7512 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-798830
Identification Number:	10.3389/fcimb.2025.1671738
Journal or Publication Title:	Frontiers in Cellular and Infection Microbiology
Volume:	15
Date:	23 September 2025
Publisher:	Frontiers
ISSN:	2235-2988
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Mathematics and Natural Sciences Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry Faculty of Medicine > Biochemie > Zentrum für Biochemie Faculty of Medicine > Kinder- und Jugendmedizin > Klinik und Poliklinik für Kinder- und Jugendmedizin Faculty of Medicine > Klinische Chemie > Institut für Klinische Chemie Faculty of Medicine > Orthopädie > Klinik und Poliklinik für Orthopädie und Unfallchirurgie Faculty of Medicine > Zahn-, Mund- und Kieferheilkunde > Institut für experimentelle Zahnmedizin und orale muskuloskeletale Biologie Zentrum für Molekulare Medizin
Subjects:	Chemistry and allied sciences Life sciences Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79883