Liushen Capsules, a promising clinical candidate for COVID-19, alleviates SARS-CoV-2-induced pulmonary in vivo and inhibits the proliferation of the variant virus strains in vitro.
Liushen Capsules, a promising clinical candidate for COVID-19, alleviates SARS-CoV-2-induced pulmonary in vivo and inhibits the proliferation of the variant virus strains in vitro.
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Liushen胶囊是COVID-19的有前途的临床候选者，可以减轻体内SARS-COV-2诱导的肺部，并抑制体外变异病毒菌株的增殖。
DOI：
10.1186/s13020-022-00598-4
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发表时间：
2022-04-01
期刊：
影响因子：
4.9
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Ma Q;Lei B;Chen R;Liu B;Lu W;Jiang H;Chen Z;Guo X;Wang Y;Zhang L;Chen Q;Li X;Yang Z
2019年冠状病毒病（COVID-19）导致全球大流行，并在世界各地造成破坏性影响，然而，对于SARS-CoV-2的不断突变，没有特异性的抗病毒药物和疫苗。本研究通过体外抗新型冠状病毒、抗炎作用、对新型SARS-CoV-2感染小鼠的治疗作用及临床疗效观察，观察六神胶囊对新型冠状病毒的临床疗效及安全性。体外实验观察LS对501Y.V_2/B.1.35和G/478K.V_1/ B.1.617.2的抗病毒和抗炎作用。建立新型SARS-CoV-2肺炎hACE 2小鼠模型。采用免疫组化和Western blotting方法检测各组大鼠的存活率、肺组织病理学改变、炎性指标、肺组织病毒滴度和NF-κB/MAPK信号通路中关键蛋白的表达。以病程、预后、核酸转阴时间、血清细胞因子水平等指标评价LS治疗的疗效。结果表明，LS（2、1、0.5 μg/mL）能显著抑制SARS-CoV-2变异株的复制和病毒诱导的促炎细胞因子（IL-6、IL-8、IP-10、CCL-5、MIP-1α、IL-1α）的表达。在小鼠存活实验中，病毒组的存活率为20%，而LS（40、80、160 mg/kg）处理组的存活率分别提高到60、100、100%。LS（40、80、160 mg/kg）能显著降低小鼠肺组织滴度，改善肺组织病理学改变，抑制炎症介质（IFN-α、IFN-γ、IP-10、MCP-1）的过度分泌和p-NF-κB p65蛋白的表达。LS还能显著降低SARS-CoV-2诱导的p-NF-κB p65、p-IκBα和p-p38 MAPK的活化，增加IκBα的蛋白表达。此外，患者在接受LS治疗6天后症状完全缓解，并在治疗23天后PCR检测结果为阴性。最后，LS治疗可减少炎性细胞因子（IL-6、PDGF-AA/BB、Eotaxin、MCP-1、MIP-1α、MIP-1β、GRO、CCL-5、MCP-3、IP-10、IL-1α）的释放。LS在体外和体内有效缓解新型SARS-CoV-2或变种诱导的肺炎，改善COVID-19的预后。根据疗效和安全性特征，LS可被考虑用于治疗COVID-19，并使用广谱抗病毒和抗炎剂。
Coronavirus disease 2019 (COVID-19) causes a global pandemic and has devastating effects around the world, however, there are no specific antiviral drugs and vaccines for the constant mutation of SARS-CoV-2. In this study, we evaluted the antiviral and anti-inflammatory activities of Liushen Capsules (LS) on different novel coronavirus in vitro, studied its therapeutic effects on novel SARS-CoV-2 infected mice and observed the LS’s clinical efficacy and safety in COVID-19. The antiviral and aiti-inflammatory effects of LS on the 501Y.V2/B.1.35 and G/478K.V1/ B.1.617.2 strains were determined in vitro. A hACE2 mouse model of novel SARS-CoV-2 pneumonia was established. Survival rates, histological changes, inflammatory markers, lung virus titers and the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blotting and immumohistochemical staining in the lungs were measured. Subsequently, the disease duration, prognosis of disease, time of negative nucleic acid and the cytokines levels in serum were used to assess the efficacy of treatment with LS in patients. The results showed that LS (2, 1, 0.5 μg/mL) could significantly inhibit the replication of the two SARS-CoV-2 variants and the expression of pro-inflammatory cytokines (IL-6, IL-8, IP-10, CCL-5, MIP-1α, IL-1α) induced by the virus in vitro. As for the survival experiment in mice, the survival rate of virus group was 20%, while LS-treatment groups (40, 80, 160 mg/kg) could increase the survival rate to 60, 100 and 100%, respectively. LS (40, 80, 160 mg/kg) could significantly decrease the lung titers in mice and it could improve the pathological changes, inhibit the excessive inflammatory mediators (IFN-α, IFN-γ, IP-10, MCP-1) and the protein expression of p-NF-κB p65 in mice. Moreover, LS could significantly decrease SARS-CoV-2-induced activation of p-NF-κB p65, p-IκBα, and p-p38 MAPK and increase the protein expression of the IκBα. In addition, the patient got complete relief of symptoms after being treated with LS for 6 days and was proven with negative PCR test after being treated for 23 days. Finally, treatment with LS could reduce the release of inflammatory cytokines (IL-6, PDGF-AA/BB, Eotaxin, MCP-1, MIP-1α, MIP-1β, GRO, CCL-5, MCP-3, IP-10, IL-1α). LS effectively alleviated novel SARS-CoV-2 or variants induced pneumonia in vitro and in vivo, and improved the prognosis of COVID-19. In light of the efficacy and safety profiles, LS could be considered for the treatment of COVID-19 with a broad-spectrum antiviral and anti-inflammatory agent.
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DOI：
10.1186/s10020-020-00230-x
发表时间：
2020-10-29
期刊：
Molecular medicine (Cambridge, Mass.)
影响因子：
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