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PLNC8 αβ Potently Inhibits the Flavivirus Kunjin and Modulates Inflammatory and Intracellular Signaling Responses of Alveolar Epithelial Cells
Örebro University, School of Medical Sciences.ORCID iD: 0000-0002-0351-976X
School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Örebro University, School of Medical Sciences.ORCID iD: 0000-0001-5939-2932
Örebro University, School of Medical Sciences.ORCID iD: 0000-0001-9876-6239
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2024 (English)In: Viruses, E-ISSN 1999-4915, Vol. 16, no 11, article id 1770Article in journal (Refereed) Published
Abstract [en]

PLNC8 alpha beta is a cationic antimicrobial peptide that previously has been reported to express both antibacterial and antiviral properties. This study aimed to further elucidate the antiviral effects of PLNC8 alpha beta and its impact on virus-induced cytotoxicity and inflammatory signaling in human alveolar epithelial cells (A549) infected with the flavivirus Kunjin. Complementary in silico analyses using molecular dynamics (MD) simulation were conducted to investigate the mechanism of action of PLNC8 alpha beta by studying the interaction of PLNC8 alpha and beta with models of a flavivirus membrane and a eukaryotic plasma membrane, respectively. Our findings demonstrated that PLNC8 alpha beta significantly reduces both extracellular and intracellular viral loads, as confirmed by plaque reduction assays and RT-PCR. The peptide also mitigated virus-induced cytotoxicity and inflammation. Notably, PLNC8 alpha beta modulated the virus-induced dysregulation of key signaling and inflammatory genes, such as TLR9, TLR3, NOD2, FOS, JUN, IL6, and CXCL8. MD simulation revealed that PLNC8 alpha beta exhibits higher binding affinity for a flavivirus membrane model compared to a model of the plasma membrane, likely due to stronger electrostatic interactions with anionic phospholipids. This selective interaction possibly accounts for a potent antiviral activity of PLNC8 alpha beta combined with a minimal cytotoxicity toward human cells. Overall, PLNC8 alpha beta shows significant promise as an antiviral agent against flavivirus infections and warrants further exploration for peptide-based antiviral therapies.

Place, publisher, year, edition, pages
MDPI , 2024. Vol. 16, no 11, article id 1770
Keywords [en]
PLNC8 alpha beta, antiviral, flavivirus, inflammation, MD simulation
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:oru:diva-117678DOI: 10.3390/v16111770ISI: 001366566900001PubMedID: 39599884Scopus ID: 2-s2.0-85210268538OAI: oai:DiVA.org:oru-117678DiVA, id: diva2:1919365
Funder
Knowledge Foundation, 20180148Available from: 2024-12-09 Created: 2024-12-09 Last updated: 2024-12-09Bibliographically approved

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Omer, Abubakr A. M.Söderquist, BoMelik, WessamBengtsson, TorbjörnKhalaf, Hazem

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Viruses
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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