Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy

Porcine epidemic diarrhea virus (PEDV) is a harmful coronavirus infecting pigs, which is resulting in substantial financial losses in the global pig industry. The lack of effective vaccines or treatments underscores the pressing need for new antiviral strategies. Antimicrobial peptides (AMPs), speci...

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Main Authors: Fatemeh Pashaie, Tabitha E. Hoornweg, Floris J. Bikker, Tineke Veenendaal, Femke Broere, Edwin J.A. Veldhuizen
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Virus Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0168170224001898
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author Fatemeh Pashaie
Tabitha E. Hoornweg
Floris J. Bikker
Tineke Veenendaal
Femke Broere
Edwin J.A. Veldhuizen
author_facet Fatemeh Pashaie
Tabitha E. Hoornweg
Floris J. Bikker
Tineke Veenendaal
Femke Broere
Edwin J.A. Veldhuizen
author_sort Fatemeh Pashaie
collection DOAJ
description Porcine epidemic diarrhea virus (PEDV) is a harmful coronavirus infecting pigs, which is resulting in substantial financial losses in the global pig industry. The lack of effective vaccines or treatments underscores the pressing need for new antiviral strategies. Antimicrobial peptides (AMPs), specifically cathelicidins such as LL-37, have demonstrated promising activity against a range of viruses. This study aims to elucidate the antiviral mechanisms of cathelicidins by examining their inhibitory capabilities against PEDV in vitro. Four pig-derived antimicrobial peptides (PMAP-36, PMAP-23, PR-39, and PG-1), together with chicken-derived CATH-B1 and human-derived LL-37 were analyzed for their anti-PEDV activity. Flow cytometry and fluorescent microscopy confirmed that LL-37 and CATH-B1 had strong inhibitory effects at non-toxic concentrations of 5 and 10 µM, significantly reducing GFP-PEDV infection of Vero cells both in co- and pre-incubation setups. In contrast, none of the porcine peptides exhibited any inhibitory effects, even at higher doses. Fluorogenic LL-37 was shown to enter VERO cells, indicative of a possible immunomodulatory antiviral mode of action. However, transmission electron microscopy clearly indicated that both LL-37 and CATH-B1 affected virus morphology and caused aggregation of viral particles, showing that peptide-virus interaction caused reduced virus infectivity. In conclusion, this analysis highlights the potential of LL-37 and CATH-B1 as inhibitors against PEDV, suggesting promising directions for innovative therapeutic antiviral strategies.
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spelling doaj-art-794bca7643614e2ebe50717178ceddbc2025-08-20T01:58:08ZengElsevierVirus Research1872-74922024-12-0135019949610.1016/j.virusres.2024.199496Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacyFatemeh Pashaie0Tabitha E. Hoornweg1Floris J. Bikker2Tineke Veenendaal3Femke Broere4Edwin J.A. Veldhuizen5Department of Biomolecular Health Sciences, Division Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, the NetherlandsDepartment of Biomolecular Health Sciences, Division Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, the NetherlandsDepartment of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam 1081 LA, the NetherlandsCell Microscopy Core, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584CX, the NetherlandsDepartment of Biomolecular Health Sciences, Division Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, the NetherlandsDepartment of Biomolecular Health Sciences, Division Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, the Netherlands; Corresponding author.Porcine epidemic diarrhea virus (PEDV) is a harmful coronavirus infecting pigs, which is resulting in substantial financial losses in the global pig industry. The lack of effective vaccines or treatments underscores the pressing need for new antiviral strategies. Antimicrobial peptides (AMPs), specifically cathelicidins such as LL-37, have demonstrated promising activity against a range of viruses. This study aims to elucidate the antiviral mechanisms of cathelicidins by examining their inhibitory capabilities against PEDV in vitro. Four pig-derived antimicrobial peptides (PMAP-36, PMAP-23, PR-39, and PG-1), together with chicken-derived CATH-B1 and human-derived LL-37 were analyzed for their anti-PEDV activity. Flow cytometry and fluorescent microscopy confirmed that LL-37 and CATH-B1 had strong inhibitory effects at non-toxic concentrations of 5 and 10 µM, significantly reducing GFP-PEDV infection of Vero cells both in co- and pre-incubation setups. In contrast, none of the porcine peptides exhibited any inhibitory effects, even at higher doses. Fluorogenic LL-37 was shown to enter VERO cells, indicative of a possible immunomodulatory antiviral mode of action. However, transmission electron microscopy clearly indicated that both LL-37 and CATH-B1 affected virus morphology and caused aggregation of viral particles, showing that peptide-virus interaction caused reduced virus infectivity. In conclusion, this analysis highlights the potential of LL-37 and CATH-B1 as inhibitors against PEDV, suggesting promising directions for innovative therapeutic antiviral strategies.http://www.sciencedirect.com/science/article/pii/S0168170224001898Antimicrobial peptidesCathelicidinsAntiviral activityPorcine epidemic diarrhea virusVero cells
spellingShingle Fatemeh Pashaie
Tabitha E. Hoornweg
Floris J. Bikker
Tineke Veenendaal
Femke Broere
Edwin J.A. Veldhuizen
Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy
Virus Research
Antimicrobial peptides
Cathelicidins
Antiviral activity
Porcine epidemic diarrhea virus
Vero cells
title Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy
title_full Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy
title_fullStr Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy
title_full_unstemmed Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy
title_short Antiviral activity of cathelicidins against porcine epidemic diarrhea virus (PEDV): Mechanisms, and efficacy
title_sort antiviral activity of cathelicidins against porcine epidemic diarrhea virus pedv mechanisms and efficacy
topic Antimicrobial peptides
Cathelicidins
Antiviral activity
Porcine epidemic diarrhea virus
Vero cells
url http://www.sciencedirect.com/science/article/pii/S0168170224001898
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