Cheng Sheng, Xin Jialiang, Zhang Tianran, Zhang Yulin, Ji Chengxi, Kang Lulu, Zhu Xiangyu, Zhang He, Wang Wei, Liao Xinfei
Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
The Humanities Laboratory for Ecological Civilization and Environmental Governance of Zhejiang Province, Institute of Virology, Wenzhou University, Wenzhou, China.
Front Cell Infect Microbiol. 2025 Jul 22;15:1623860. doi: 10.3389/fcimb.2025.1623860. eCollection 2025.
Chikungunya virus (CHIKV) infection is often linked to acute interstitial nephritis (AIN) in fatal cases. Given the global spread of CHIKV and the lack of targeted antiviral treatments, there is an urgent need for effective therapeutic strategies against CHIKV-induced AIN. This study explored the therapeutic potential of salidroside (Sal) using an integrative approach involving network pharmacology, molecular docking and validation. Network pharmacology analysis identified 18 overlapping targets between Sal and AIN, including TNF, IL6 and AKT1. Molecular docking revealed strong binding affinities between Sal and key pathway proteins (Vina scores < -6), notably TNF, IL6 and BCL2. assays using CHIKV-infected 293T cells demonstrated that Sal (7.8125-2000 μM) enhanced cell viability by 8.9-25.9%, with the greatest effect observed at 1000 μM, without significantly altering viral replication. Mechanism analysis using the KEGG and FerrDB databases implicated apoptosis and ferroptosis in CHIKV-induced AIN pathogenesis. RT-qPCR analysis confirmed that Sal significantly downregulated ferroptosis-related genes (IL-6, IL-1β, SIRT1, PARP1, HMOX1) and apoptosis-associated markers (Bax, TNF-α, PARP1) in infected cells. Consistent with these findings, molecular docking demonstrated that Sal binds strongly to the ferroptosis-related protein GPX4 (Vina score: -6.3) and the apoptosis regulator NFKB1 (Vina score: -6.0). These results suggest that Sal is a promising therapeutic candidate for the treatment of CHIKV-induced AIN.
基孔肯雅病毒（CHIKV）感染在致死病例中常与急性间质性肾炎（AIN）相关。鉴于CHIKV的全球传播以及缺乏针对性的抗病毒治疗方法，迫切需要针对CHIKV诱导的AIN的有效治疗策略。本研究采用网络药理学、分子对接和验证相结合的方法，探索了红景天苷（Sal）的治疗潜力。网络药理学分析确定了Sal和AIN之间的18个重叠靶点，包括TNF、IL6和AKT1。分子对接显示Sal与关键通路蛋白之间具有很强的结合亲和力（Vina评分＜-6），特别是TNF、IL6和BCL2。使用CHIKV感染的293T细胞进行的实验表明，Sal（7.8125 - 2000 μM）可使细胞活力提高8.9 - 25.9%，在1000 μM时效果最佳，且未显著改变病毒复制。使用KEGG和FerrDB数据库进行的机制分析表明，凋亡和铁死亡参与了CHIKV诱导的AIN发病机制。RT-qPCR分析证实，Sal显著下调了感染细胞中铁死亡相关基因（IL-6、IL-1β、SIRT1、PARP1、HMOX1）和凋亡相关标志物（Bax、TNF-α、PARP1）。与这些发现一致，分子对接表明Sal与铁死亡相关蛋白GPX4（Vina评分：-6.3）和凋亡调节因子NFKB1（Vina评分：-6.0）紧密结合。这些结果表明，Sal是治疗CHIKV诱导的AIN的有前景的治疗候选药物。
