Balsera-Manzanero María, Soengas Raquel G, Carretero-Ledesma Marta, Ratia Carlos, Iglesias M José, Pachón Jerónimo, López-Ortiz Fernando, Cordero Elisa, Soto Sara M, Sánchez-Céspedes Javier
Unidad Clínica de Enfermedades Infecciosas, Microbiología y Parasitología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Área de Química Orgánica, Centro de Investigación CIAIMBITAL, Universidad de Almería, Spain.
Heliyon. 2024 Mar 19;10(6):e27601. doi: 10.1016/j.heliyon.2024.e27601. eCollection 2024 Mar 30.
Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we report the anti-HAdV activity of sub-micromolar concentrations of four heteroleptic (C^S)-cycloaurated complexes bearing a single thiophosphinamide [, , and ] or thiophosphonamide [] chelating ligand and a dithiocarbamate moiety. In addition to their low cytotoxicity, the findings of mechanistic assays revealed that these molecules have antiviral activity by targeting stages of the viral replication cycle subsequent to DNA replication. Additionally, all four compounds showed a significant inhibition of human cytomegalovirus (HCMV) DNA replication, thereby providing evidence for potential broad-spectrum antiviral activity.
尽管腺病毒(HAdV)感染在健康个体中的临床影响日益广泛,且在免疫抑制患者中,尤其是儿科人群中具有较高的发病率,但针对这种病毒的特异性治疗方法尚未开发出来。在本研究中,我们报告了四种具有单个硫代磷酰胺[、和]或硫代磷酰亚胺[]螯合配体以及二硫代氨基甲酸盐部分的亚微摩尔浓度的杂配(C^S)-环金配合物的抗HAdV活性。除了低细胞毒性外,机理分析结果表明,这些分子通过靶向DNA复制后的病毒复制周期阶段而具有抗病毒活性。此外,所有四种化合物均对人巨细胞病毒(HCMV)DNA复制表现出显著抑制作用,从而为潜在的广谱抗病毒活性提供了证据。