Dong Zhongwei, Wang Xinyu, Hu Gaowei, Huang Qingye, Zhang Yulin, Jia Yuping, Du Shujuan, Zhu Caixia, Wei Fang, Zhang Daizhou, Wang Yuyan, Cai Qiliang
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, Shanghai Institute of Infections Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Shandong Academy of Pharmaceutical Sciences, Jinan, People's Republic of China.
Emerg Microbes Infect. 2025 Dec;14(1):2440490. doi: 10.1080/22221751.2024.2440490. Epub 2024 Dec 19.
The Coronavirus Disease 2019 (COVID-19) pandemic has led to numerous cases of co-infection with SARS-CoV-2 and other viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), worldwide. This co-infection has increased patient mortality due to the lack of efficient bi-targeted drugs. Cambogin, a bioactive natural product, has been shown to effectively induce regression of KSHV-latently infected tumours in xenograft mice models; however, its impact on SARS-CoV-2 infection remains unclear. Here, we report that Cambogin targets 46 host genes commonly affected by both SARS-CoV-2 and KSHV infections, as identified through bioinformatics analysis. These genes are related with 14 key upstream signalling pathways, particularly those involved in inflammation regulation, protein phosphorylation, metabolic processes, and cellular stress response. Within the transcriptional factor (TF)-miRNA co-regulatory network, ten out of 46 hub-target genes are closely linked to Cambogin and KSHV/SARS-CoV-2. Importantly, Cambogin not only efficiently blocks the replication and virion production of SARS-CoV-2 and by reducing the expression of EGFR and Cyclin A2, but also simultaneously inhibits both SARS-CoV-2 infection and the growth of KSHV-induced tumours using a murine xenograft model. These findings provide an alternative strategy for the potential use of Cambogin in the treatment of SARS-CoV-2 patients, particularly those with KSHV co-infection.
2019年冠状病毒病（COVID-19）大流行在全球范围内导致了许多严重急性呼吸综合征冠状病毒2（SARS-CoV-2）与其他病毒的合并感染病例，包括卡波西肉瘤相关疱疹病毒（KSHV）。由于缺乏有效的双靶点药物，这种合并感染增加了患者死亡率。藤黄菌素是一种生物活性天然产物，已被证明能在异种移植小鼠模型中有效诱导KSHV潜伏感染肿瘤的消退；然而，其对SARS-CoV-2感染的影响仍不清楚。在此，我们报告通过生物信息学分析确定，藤黄菌素靶向46个受SARS-CoV-2和KSHV感染共同影响的宿主基因。这些基因与14条关键上游信号通路相关，特别是那些参与炎症调节、蛋白质磷酸化、代谢过程和细胞应激反应的通路。在转录因子（TF）-微小RNA（miRNA）共调控网络中，46个中心靶点基因中有10个与藤黄菌素和KSHV/SARS-CoV-2密切相关。重要的是，藤黄菌素不仅通过降低表皮生长因子受体（EGFR）和细胞周期蛋白A2的表达有效阻断SARS-CoV-2的复制和病毒粒子产生，还使用小鼠异种移植模型同时抑制SARS-CoV-2感染和KSHV诱导肿瘤的生长。这些发现为藤黄菌素在治疗SARS-CoV-2患者，特别是合并KSHV感染的患者中的潜在应用提供了一种替代策略。
