Wang Wenlei, Zheng Zhihui, Qi Xiaoyuan, Wei Hailin, Mao Xuhua, Su Qin, Chen Xiang, Feng Yan, Qiao Guohong, Ma Tieliang, Tang Zhian, Zhou Guangming, Zhuang Jinqiang, Zhang Pinghu
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou, China.
National Human Diseases Animal Model Resource Center, NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Science and Peking Union Medical School, Beijing, China.
Front Pharmacol. 2024 Sep 16;15:1431617. doi: 10.3389/fphar.2024.1431617. eCollection 2024.
Fufang Yinhua Jiedu (FFYH) granules are recommended for treating coronavirus pneumonia (COVID-19) in China. However, its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity and clinical efficacy against COVID-19 remain to be confirmed.
Our study aimed to investigate the anti-SARS-CoV-2 effect and potential mechanism of FFYH.
The activity of FFYH against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated via cell pathogenic effects, immunoblotting, immunofluorescence staining, and qRT-PCR. The potential mechanism of FFYH against SARS-CoV-2 was investigated by immunoblotting. One head-to-head randomized controlled trial was designed to evaluate the clinical efficacy of FFYH in mild COVID-19. Two hundred patients were randomly recruited to receive either FFYH or LHQW (Lianhua Qingwen) granules.
The results indicated that FFYH effectively inhibited SARS-CoV-2 replication by suppressing CPE and decreasing viral RNA and protein expression. A time-of-drug-addition assay confirmed that FFYH mainly targeted the binding and replication stages of the SARS-CoV-2 life cycle. Mechanistic studies revealed that blocking SARS-CoV-2-triggered autophagy may be the primary mechanism by which FFYH protects against SARS-CoV-2 infection by regulating the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Clinical results confirmed that FFYH effectively shortened the recovery time of clinical symptoms and viral nucleic acid negativity, improved abnormal hematology parameters, and controlled excessive cytokine responses in mild COVID-19 patients. Subgroup analysis revealed that FFYH improved the recovery time of clinical symptoms, improved hematological parameters, and controlled excessive cytokine storms to a greater extent in the mild COVID-19 male subgroup, abnormal hematology subgroup, and 32-42-year-old subgroup than in the corresponding LHQW subgroup ( < 0.05). No patients progressed to severe or critical cases.
Our results indicate that FFYH not only has good anti-viral activity against SARS-CoV-2 but also has significant efficacy against COVID-19, indicating that FFYH may be a novel complementary option for treating COVID-19.
在中国，复方银花解毒颗粒被推荐用于治疗新型冠状病毒肺炎（COVID-19）。然而，其抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）活性及对COVID-19的临床疗效仍有待证实。
本研究旨在探究复方银花解毒颗粒抗SARS-CoV-2的作用及潜在机制。
通过细胞病变效应、免疫印迹、免疫荧光染色及qRT-PCR评估复方银花解毒颗粒对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的活性。通过免疫印迹研究复方银花解毒颗粒抗SARS-CoV-2的潜在机制。设计一项头对头随机对照试验以评估复方银花解毒颗粒对轻症COVID-19的临床疗效。随机招募200例患者，分别给予复方银花解毒颗粒或连花清瘟颗粒。
结果表明，复方银花解毒颗粒通过抑制细胞病变效应及降低病毒RNA和蛋白表达有效抑制SARS-CoV-2复制。药物添加时间试验证实，复方银花解毒颗粒主要作用于SARS-CoV-2生命周期的结合和复制阶段。机制研究表明，阻断SARS-CoV-2引发的自噬可能是复方银花解毒颗粒通过调节磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素靶蛋白（mTOR）信号通路预防SARS-CoV-2感染的主要机制。临床结果证实，复方银花解毒颗粒有效缩短了轻症COVID-19患者临床症状的恢复时间及病毒核酸转阴时间，改善了血液学异常参数，并控制了过度的细胞因子反应。亚组分析显示，在轻症COVID-19男性亚组、血液学异常亚组及32-42岁亚组中，复方银花解毒颗粒在改善临床症状恢复时间、改善血液学参数及控制过度细胞因子风暴方面比相应的连花清瘟颗粒亚组更显著（P<0.05）。无患者进展为重症或危重症病例。
我们的结果表明，复方银花解毒颗粒不仅对SARS-CoV-2具有良好的抗病毒活性，而且对COVID-19具有显著疗效，提示复方银花解毒颗粒可能是治疗COVID-19的一种新型补充选择。
