Uncovering the Anti-Herpetic Activity of Anionic Peptides Derived From the Cytoplasmic Domain of Nectin-1
Nectin-1/herpes simplex virus glycoprotein D (HSV gD) interaction is crucial to drive herpes simplex virus (HSV) entry. Polyanions are known to show great potential as antivirals. Thus, we explored a peptide-based biotherapeutic approach and, for the first time, evaluated an anionic peptide derived...
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SAGE Publishing
2025-06-01
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| Series: | Bioinformatics and Biology Insights |
| Online Access: | https://doi.org/10.1177/11779322251344130 |
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| author | Rakesh Rahangdale Sumit Birangal Gautham Shenoy Fayaz Shaik Mohammad Mukesh Pasupuleti Raghu Chandrashekar Hariharapura |
| author_facet | Rakesh Rahangdale Sumit Birangal Gautham Shenoy Fayaz Shaik Mohammad Mukesh Pasupuleti Raghu Chandrashekar Hariharapura |
| author_sort | Rakesh Rahangdale |
| collection | DOAJ |
| description | Nectin-1/herpes simplex virus glycoprotein D (HSV gD) interaction is crucial to drive herpes simplex virus (HSV) entry. Polyanions are known to show great potential as antivirals. Thus, we explored a peptide-based biotherapeutic approach and, for the first time, evaluated an anionic peptide derived from nectin-1 designed to bind HSV gD. Peptides enriched in acidic and basic residues were selected and computationally modeled using PEP-FOLD3, PROCHECK, ClusPro 2.0, and Desmond. Their antiviral efficacy was tested through virucidal, cell pretreatment, attachment inhibition, entry inhibition, and cytopathic effect (CPE) inhibition assays using a 10 TCID 50 (Tissue Culture Infectious Dose 50%) viral dose. Among 4 designed peptides, C1 and C2 showed strong binding to HSV-1 and HSV-2 gD in molecular dynamic (MD) simulations. Peptide C1 exhibited significant virucidal activity (HSV-1: 64.92%, HSV-2: 67.16%), attachment inhibition (HSV-1: 62.03%, HSV-2: 59.38%), and host cell-entry inhibition (HSV-1: 71.37%, HSV-2: 76.28%) at 250 µg/mL concentration. Combination treatment with peptides C1 and C2 at a final concentration of 250 µg/mL (125 µg/mL each) exhibited an additive effect against HSV-1 (68.57%) and HSV-2 (73.37%) infections when tested by CPE inhibition assay. This highlights the potential of HSV gD-targeted anionic peptides for future anti-HSV therapeutics. |
| format | Article |
| id | doaj-art-a1684daa8ebc4890a70a5baa76a17093 |
| institution | OA Journals |
| issn | 1177-9322 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Bioinformatics and Biology Insights |
| spelling | doaj-art-a1684daa8ebc4890a70a5baa76a170932025-08-20T02:10:23ZengSAGE PublishingBioinformatics and Biology Insights1177-93222025-06-011910.1177/11779322251344130Uncovering the Anti-Herpetic Activity of Anionic Peptides Derived From the Cytoplasmic Domain of Nectin-1Rakesh Rahangdale0Sumit Birangal1Gautham Shenoy2Fayaz Shaik Mohammad3Mukesh Pasupuleti4Raghu Chandrashekar Hariharapura5Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, IndiaDepartment of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, IndiaDepartment of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, IndiaDepartment of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaDepartment of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, IndiaNectin-1/herpes simplex virus glycoprotein D (HSV gD) interaction is crucial to drive herpes simplex virus (HSV) entry. Polyanions are known to show great potential as antivirals. Thus, we explored a peptide-based biotherapeutic approach and, for the first time, evaluated an anionic peptide derived from nectin-1 designed to bind HSV gD. Peptides enriched in acidic and basic residues were selected and computationally modeled using PEP-FOLD3, PROCHECK, ClusPro 2.0, and Desmond. Their antiviral efficacy was tested through virucidal, cell pretreatment, attachment inhibition, entry inhibition, and cytopathic effect (CPE) inhibition assays using a 10 TCID 50 (Tissue Culture Infectious Dose 50%) viral dose. Among 4 designed peptides, C1 and C2 showed strong binding to HSV-1 and HSV-2 gD in molecular dynamic (MD) simulations. Peptide C1 exhibited significant virucidal activity (HSV-1: 64.92%, HSV-2: 67.16%), attachment inhibition (HSV-1: 62.03%, HSV-2: 59.38%), and host cell-entry inhibition (HSV-1: 71.37%, HSV-2: 76.28%) at 250 µg/mL concentration. Combination treatment with peptides C1 and C2 at a final concentration of 250 µg/mL (125 µg/mL each) exhibited an additive effect against HSV-1 (68.57%) and HSV-2 (73.37%) infections when tested by CPE inhibition assay. This highlights the potential of HSV gD-targeted anionic peptides for future anti-HSV therapeutics.https://doi.org/10.1177/11779322251344130 |
| spellingShingle | Rakesh Rahangdale Sumit Birangal Gautham Shenoy Fayaz Shaik Mohammad Mukesh Pasupuleti Raghu Chandrashekar Hariharapura Uncovering the Anti-Herpetic Activity of Anionic Peptides Derived From the Cytoplasmic Domain of Nectin-1 Bioinformatics and Biology Insights |
| title | Uncovering the Anti-Herpetic Activity of Anionic Peptides Derived From the Cytoplasmic Domain of Nectin-1 |
| title_full | Uncovering the Anti-Herpetic Activity of Anionic Peptides Derived From the Cytoplasmic Domain of Nectin-1 |
| title_fullStr | Uncovering the Anti-Herpetic Activity of Anionic Peptides Derived From the Cytoplasmic Domain of Nectin-1 |
| title_full_unstemmed | Uncovering the Anti-Herpetic Activity of Anionic Peptides Derived From the Cytoplasmic Domain of Nectin-1 |
| title_short | Uncovering the Anti-Herpetic Activity of Anionic Peptides Derived From the Cytoplasmic Domain of Nectin-1 |
| title_sort | uncovering the anti herpetic activity of anionic peptides derived from the cytoplasmic domain of nectin 1 |
| url | https://doi.org/10.1177/11779322251344130 |
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