Manie Esraa A, Elzayat Emad M, Ragab Sherif S, Sweed Ayman M, Ibrahim Hosny, Nasser Sherif, Allayeh Abdou K
Biotechnology Program, Faculty of Science, Cairo University, Dokki, Giza, Egypt.
Department of Biotechnology, Faculty of Science, Cairo University, Dokki, Giza, Egypt.
Virol J. 2025 Apr 11;22(1):97. doi: 10.1186/s12985-025-02707-9.
In recent decades, viral outbreaks have significantly threatened global health, with herpes simplex virus type 2 (HSV-2) being one of the most prevalent infections. This study evaluated novel spiropyrimidine derivatives as potential antiviral agents against HSV-2, building on previous research that examined spirocyclic thiopyrimidinone derivatives against human coronavirus 229E (hCoV-229E). Among the eleven synthesized compounds, spiropyrimidinone derivative 3 demonstrated promising antiviral activity, with a selectivity index of 11.2. The drug mechanism of infection studies indicated that compound 3 primarily inhibits HSV-2 at the viral adsorption stage, achieving approximately 83% inhibition and reducing viral multiplication by 34%. Its efficacy is linked to its diketone moiety, which is known for its ability to enhance antiviral effects. Furthermore, the effect of compound 3 on viral inhibition is reflected in the level of caspase-3 protein expression, revealing that the apoptotic pathway is modulated. Docking studies revealed multiple interactions with herpes virus entry mediator (HVEM), indicating its potential as an entry inhibitor. These findings confirm that compound 3 could be a potential candidate for further development in HSV-2 antiviral therapy.
近几十年来，病毒爆发严重威胁全球健康，其中2型单纯疱疹病毒（HSV - 2）是最普遍的感染之一。本研究基于先前研究螺环噻嘧啶酮衍生物对人冠状病毒229E（hCoV - 229E）的研究，评估新型螺嘧啶衍生物作为抗HSV - 2的潜在抗病毒药物。在合成的11种化合物中，螺嘧啶酮衍生物3表现出有前景的抗病毒活性，选择性指数为11.2。感染的药物作用机制研究表明，化合物3主要在病毒吸附阶段抑制HSV - 2，实现约83%的抑制率，并使病毒增殖降低34%。其疗效与其二酮部分有关，该部分以增强抗病毒作用的能力而闻名。此外，化合物3对病毒抑制的作用反映在半胱天冬酶 - 3蛋白表达水平上，表明凋亡途径受到调节。对接研究揭示了与疱疹病毒进入介质（HVEM）的多种相互作用，表明其作为进入抑制剂的潜力。这些发现证实化合物3可能是HSV - 2抗病毒治疗进一步开发的潜在候选药物。
