Rahangdale Rakesh, Birangal Sumit, Shenoy Gautham, Mohammad Fayaz Shaik, Pasupuleti Mukesh, Hariharapura Raghu Chandrashekar
Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India.
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India.
Bioinform Biol Insights. 2025 Jun 21;19:11779322251344130. doi: 10.1177/11779322251344130. eCollection 2025.
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 (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.
Nectin-1/单纯疱疹病毒糖蛋白D（HSV gD）相互作用对于驱动单纯疱疹病毒（HSV）进入细胞至关重要。已知聚阴离子作为抗病毒药物具有巨大潜力。因此，我们探索了一种基于肽的生物治疗方法，并首次评估了一种源自Nectin-1的旨在结合HSV gD的阴离子肽。选择了富含酸性和碱性残基的肽，并使用PEP-FOLD3、PROCHECK、ClusPro 2.0和Desmond进行了计算建模。通过使用10个组织培养感染剂量50%（TCID）的病毒剂量进行杀病毒、细胞预处理、附着抑制、进入抑制和细胞病变效应（CPE）抑制试验来测试它们的抗病毒功效。在4种设计的肽中，C1和C2在分子动力学（MD）模拟中显示出与HSV-1和HSV-2 gD的强结合。肽C1在250μg/mL浓度下表现出显著的杀病毒活性（HSV-1：64.92%，HSV-2：67.16%）、附着抑制（HSV-1：62.03%，HSV-2：59.38%）和宿主细胞进入抑制（HSV-1：71.37%，HSV-2：76.28%）。当通过CPE抑制试验测试时，最终浓度为250μg/mL（每种125μg/mL）的肽C1和C 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.2联合治疗对HSV-1（68.57%）和HSV-2（73.37%）感染表现出相加作用。这突出了靶向HSV gD的阴离子肽在未来抗HSV治疗中的潜力。
