冠状病毒
化学
计算生物学
对接(动物)
作用机理
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
细胞激素风暴
药物发现
2019年冠状病毒病(COVID-19)
药理学
机制(生物学)
代谢物
人参皂苷Rg1
冠状病毒科
细胞因子
血浆蛋白结合
代谢组学
表面等离子共振
铅化合物
信号转导
离解常数
2019-20冠状病毒爆发
免疫系统
交互网络
病毒
生物化学
生物
作者
Zigang Qu,Yi Wang,Hongshan Yu,Siyu Xu
标识
DOI:10.1021/acs.jpcb.5c07771
摘要
The persistent threat of coronaviruses to global health necessitates urgent development of broad-spectrum therapeutics with high efficacy and low toxicity. Among promising candidates, ginsenoside compound K (CK)-a bioactive metabolite derived from Panax ginseng-has emerged with preliminary evidence indicating its potential anticoronavirus activity. The study integrates network pharmacology, molecular docking, molecular dynamics simulation, and surface plasmon resonance validation. A total of 226 shared targets between CK and coronaviruses were identified. Functional enrichment analysis revealed CK's involvement in critical processes such as immune regulation and key pathways including PI3K-Akt signaling and Coronavirus disease-SARS-COV-2. Protein-protein interaction analysis pinpointed four core targets: EGFR, STAT3, HSP90AA1, and ESR1, with molecular docking and dynamics simulations confirming high-affinity binding between CK and all core targets-experimental validation for EGFR showed a dissociation constant of 5.67 μM. The results demonstrate that CK exerts anticoronavirus effects through multitarget regulation, employing a dual mechanism: inhibiting viral entry via EGFR and HSP90AA1 and suppressing cytokine storms through modulation of the STAT3/ESR1-PI3K-Akt axis. This synergistic action overcomes the limitation of single-target antivirals by concurrently mitigating infection and hyperinflammation. Importantly, this work identifies HSP90AA1 and ESR1 as novel anticoronaviral targets, offering a mechanistic foundation for developing CK-based broad-spectrum therapeutics against coronaviruses.
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