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 in vitro and in vivo 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 in vivo 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.

中文翻译：

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KSHV 靶向小分子通过抑制 EGFR 和细胞周期蛋白 A2 的表达有效阻断 SARS-CoV-2 感染。


2019 年冠状病毒病 （COVID-19） 大流行已导致全球多例 SARS-CoV-2 和其他病毒合并感染病例，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，这种混合感染增加了患者的死亡率。柬埔寨蛋白是一种具有生物活性的天然产物，已被证明可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，它对 SARS-CoV-2 感染的影响仍不清楚。在这里，我们报道了 Cambogin 靶向 46 个通常受 SARS-CoV-2 和 KSHV 感染影响的宿主基因，这是通过生物信息学分析确定的。这些基因与 14 个关键的上游信号通路有关，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基因。在转录因子 （TF）-miRNA 共调节网络中，46 个枢纽靶基因中有 10 个与坎波菌素和 KSHV/SARS-CoV-2 密切相关。重要的是，Cambogin 不仅通过降低 EGFR 和细胞周期蛋白 A2 的表达在体外和体内有效阻断 SARS-CoV-2 的复制和病毒粒子产生，而且还同时使用小鼠异种移植模型抑制 SARS-CoV-2 感染和 KSHV 诱导的肿瘤在体内生长。这些发现为柬埔寨素在治疗 SARS-CoV-2 患者（尤其是 KSHV 合并感染患者）中的潜在用途提供了一种替代策略。