Scala Maria Carmina, Marchetti Magda, Landi Martina, Fantacuzzi Marialuigia, Superti Fabiana, Agamennone Mariangela, Campiglia Pietro, Sala Marina
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy.
National Centre for Innovative Technologies in Public Health, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy.
Pharmaceutics. 2025 Aug 1;17(8):1006. doi: 10.3390/pharmaceutics17081006.
Viral respiratory infections have a significant impact on global health and the economy. While vaccines are effective in preventing infection, they might not be available or sufficient when used alone and must be complemented by specific therapeutic strategies. The development of new antiviral agents is increasingly important due to the continual emergence of novel respiratory pathogens. Previously we identified bovine lactoferrin (bLf)-derived tetrapeptides and peptidomimetics that showed potent in vitro activity against the influenza A virus in the picomolar range. Inspired by these results, in this study, we evaluated the antiviral potential of these compounds against HCoV-229E, a human coronavirus that can cause severe disease in immunocompromised individuals, using a compound repositioning approach. Functional studies revealed that SK(N-Me)HS () interferes with viral entry and replication, while compound SKHS () primarily blocks infection in the early stages. Biophysical analyses confirmed the occurrence of high-affinity binding to the viral spike protein, and computational studies suggested that the compounds target a region involved in conformational changes necessary for membrane fusion. These findings highlight these compounds as promising candidates for coronavirus entry inhibition and underscore the value of compound repurposing in antiviral development.
病毒性呼吸道感染对全球健康和经济有重大影响。虽然疫苗在预防感染方面有效，但单独使用时可能无法获得或数量不足，必须辅以特定的治疗策略。由于新型呼吸道病原体不断出现，开发新的抗病毒药物变得越来越重要。此前我们鉴定出了源自牛乳铁蛋白（bLf）的四肽和拟肽，它们在皮摩尔范围内对甲型流感病毒显示出强大的体外活性。受这些结果的启发，在本研究中，我们采用化合物重新定位方法评估了这些化合物对HCoV-229E的抗病毒潜力，HCoV-229E是一种可在免疫功能低下个体中引起严重疾病的人类冠状病毒。功能研究表明，SK(N-Me)HS（）干扰病毒的进入和复制，而化合物SKHS（）主要在早期阶段阻断感染。生物物理分析证实了与病毒刺突蛋白发生高亲和力结合，计算研究表明这些化合物靶向参与膜融合所需构象变化的区域。这些发现突出了这些化合物作为冠状病毒进入抑制的有前景候选物，并强调了化合物重新定位在抗病毒药物开发中的价值。
