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      Antiviral activity of temporin-1CEb analogues against gingival infection with herpes simplex virus type 1

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          Abstract

          Introduction

          Oral herpes infections caused by herpes simplex virus type 1 (HSV-1) are one of the most common in the human population. Recently, they have been classified as an increasing problem in immunocompromised patients and those suffering from chronic inflammation of the oral mucosa and gums. Treatment mainly involves nucleoside analogues, such as acyclovir and its derivatives, which reduce virus replication and shedding. As drug-resistant strains of herpes emerge rapidly, there is a need for the development of novel anti-herpes agents. The aim of the study was to design an antiviral peptide, based on natural compounds, non-toxic to the host, and efficient against drug-resistant HSV-1. Here, we designed a lysine-rich derivative of amphibian temporin-1CEb conjugated to peptides penetrating the host cell membrane and examined their activity against HSV-1 infection of oral mucosa.

          Methods

          We assessed the antiviral efficiency of the tested compound in simple 2D cell models (VeroE6 and TIGKs cells) and a 3D organotypic model of human gingiva (OTG) using titration assay, qPCR, and confocal imaging. To identify the molecular mechanism of antiviral activity, we applied the Azure A metachromatic test, and attachment assays techniques. Toxicity of the conjugates was examined using XTT and LDH assays.

          Results

          Our results showed that temporin-1CEb analogues significantly reduce viral replication in oral mucosa. The mechanism of peptide analogues is based on the interaction with heparan sulfate, leading to the reduce attachment of HSV-1 to the cell membrane. Moreover, temporin-1CEb conjugates effectively penetrate the gingival tissue being effective against acyclovir-resistant strains. Collectively, we showed that temporin-1CEb can be regarded as a novel, naturally derived antiviral compound for HSV-1 treatment.

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          Most cited references63

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          A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS12

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            Antimicrobial host defence peptides: functions and clinical potential

            Cationic host defence peptides (CHDP), also known as antimicrobial peptides, are naturally occurring peptides that can combat infections through their direct microbicidal properties and/or by influencing the host's immune responses. The unique ability of CHDP to control infections as well as resolve harmful inflammation has generated interest in harnessing the properties of these peptides to develop new therapies for infectious diseases, chronic inflammatory disorders and wound healing. Various strategies have been used to design synthetic optimized peptides, with negligible toxicity. Here, we focus on the progress made in understanding the scope of functions of CHDP and the emerging potential clinical applications of CHDP-based therapies.
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              The immunology of host defence peptides: beyond antimicrobial activity.

              Host defence peptides (HDPs) are short, cationic amphipathic peptides with diverse sequences that are produced by various cells and tissues in all complex life forms. HDPs have important roles in the body's response to infection and inflammation. This Review focuses on human HDPs and explores the diverse immunomodulatory effects of HDPs from a systems biology perspective, which highlights the interconnected nature of the effect (or effects) of HDPs on the host. Studies have demonstrated that HDPs are expressed throughout the body and mediate a broad range of activities, which explains their association with various inflammatory diseases and autoimmune disorders. The diverse actions of HDPs, such as their roles in wound healing and in the maintenance of the microbiota, are also explored, in addition to potential therapeutic applications.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2736770/overviewRole: Role: Role: Role: Role: Role:
                Role: Role: Role: Role:
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                URI : https://loop.frontiersin.org/people/432259/overviewRole: Role: Role: Role: Role:
                Journal
                Front Oral Health
                Front Oral Health
                Front. Oral. Health
                Frontiers in Oral Health
                Frontiers Media S.A.
                2673-4842
                17 June 2024
                2024
                : 5
                : 1430077
                Affiliations
                [ 1 ]Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , Krakow, Poland
                [ 2 ]Department of Organic Chemistry, Faculty of Chemistry, University of Gdansk , Gdansk, Poland
                [ 3 ]Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, University of Louisville , Louisville, KY, United States
                Author notes

                Edited by: Georgios N. Belibasakis, Karolinska Institutet (KI), Sweden

                Reviewed by: George Hajishengallis, University of Pennsylvania, United States

                Jens Kreth, Oregon Health and Science University, United States

                [* ] Correspondence: Anna Golda anna.b.golda@ 123456uj.edu.pl Joanna Koziel joanna.koziel@ 123456uj.edu.pl
                Article
                10.3389/froh.2024.1430077
                11215077
                38953010
                f973d967-8031-4cec-8f6f-76760602e553
                © 2024 Golda, Kosikowska-Adamus, Wadowska, Dobosz, Potempa and Koziel.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 May 2024
                : 30 May 2024
                Page count
                Figures: 5, Tables: 3, Equations: 0, References: 63, Pages: 13, Words: 0
                Funding
                Funded by: National Science Centre, Poland
                Award ID: Sonata15 2019/35/D/NZ6/02154 (AG)
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article.
                The work was supported by the National Science Centre, Poland, under research Project: Sonata15 2019/35/D/NZ6/02154 (AG).
                Categories
                Oral Health
                Original Research
                Custom metadata
                Oral Infections and Microbes

                herpes simplex virus,antimicrobial peptides,temporins,heparan sulfate,gingival infection,drug-resistance

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