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冠科(GUANKE)的给药可减轻小鼠中由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的肺炎。

Administration of GUANKE alleviates SARS-CoV-2-induced pneumonia in mice.

作者信息

Huang He, Dong Xiaojing, Du Zuoyuan, Guo Li, Chen Lan, Wang Xinming, Lu Simin, Yue Kun, Ren Zhihong, Wang Jianwei, Ren Lili, Xu Jianguo

机构信息

NHC Key Laboratory of System Biology of Pathogens and Christophe Mérieux Laboratory, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

State Key Laboratory of Respiratory Health and Multimorbidity, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

出版信息

Microbiol Spectr. 2024 Oct 21;12(12):e0160324. doi: 10.1128/spectrum.01603-24.

Abstract

UNLABELLED

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets epithelial cells in the respiratory tract, triggering an acute proinflammatory response and chronic lung inflammation. Probiotic supplementation has shown promise in reducing the nasopharyngeal SARS-CoV-2 viral load, diminishing symptom frequency and duration, and mitigating inflammation; thus, it is a potential strategy for treating coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 infection. In this study, we evaluated the effects of the oral administration of the GUANKE strain, a gram-positive bacterium originally isolated from a healthy individual, on SARS-CoV-2 infection in a human ACE2 transgenic mouse model. We found that GUANKE significantly reduced inflammatory cell infiltration and pulmonary interstitial exudation in mice. The transcription of , , , and in the lungs was reduced. The protein levels of TNF-α, IL-1β, IL-6, and IL-17 in the lungs were significantly lower in GUANKE-treated mice than in control mice. The viral load in GUANKE-treated mice was lower than that in saline-treated mice, although this difference did not reach statistical significance. GUANKE can decrease SARS-CoV-2-induced lung inflammation in mice, suggesting its potential for use as an agent for treating SARS-CoV-2 infection.

IMPORTANCE

Most otherwise healthy individuals develop only mild or moderate symptoms of coronavirus disease 2019 (COVID-19) caused by current strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and virus replication is mainly confined to the upper respiratory tract; however, the virus can infect the lower respiratory tract and promote inflammation. Probiotic supplementation has been shown to reduce nasopharyngeal SARS-CoV-2 viral load, reduce the overall number and duration of symptoms, and attenuate inflammation in clinical trials. We showed that a novel GUANKE strain alleviated SARS-CoV-2-induced pneumonia in mice. The transcription and production of inflammatory cytokines were suppressed, and GUANKE moderately reduced the viral load. GUANKE has the potential to become a candidate drug for the treatment of COVID-19 or other viral respiratory infections.

摘要

未标注

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)靶向呼吸道上皮细胞,引发急性促炎反应和慢性肺部炎症。补充益生菌已显示出有望降低鼻咽部SARS-CoV-2病毒载量、减少症状发生频率和持续时间以及减轻炎症;因此,它是治疗由SARS-CoV-2感染引起的2019冠状病毒病(COVID-19)的一种潜在策略。在本研究中,我们评估了口服从一名健康个体中最初分离出的革兰氏阳性菌冠科菌株对人血管紧张素转换酶2(ACE2)转基因小鼠模型中SARS-CoV-2感染的影响。我们发现冠科菌株显著减少了小鼠的炎性细胞浸润和肺间质渗出。肺部中 、 、 、 和 的转录减少。与对照小鼠相比,经冠科菌株处理的小鼠肺部肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-17(IL-17)的蛋白水平显著更低。经冠科菌株处理的小鼠的病毒载量低于经生理盐水处理的小鼠,尽管这种差异未达到统计学显著性。冠科菌株可减轻SARS-CoV-2诱导的小鼠肺部炎症,表明其有潜力用作治疗SARS-CoV-2感染的药物。

重要性

大多数原本健康的个体感染当前的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)毒株后仅出现轻度或中度的2019冠状病毒病(COVID-19)症状,并且病毒复制主要局限于上呼吸道;然而,该病毒可感染下呼吸道并促进炎症。在临床试验中,补充益生菌已显示出可降低鼻咽部SARS-CoV-2病毒载量、减少症状总数和持续时间以及减轻炎症。我们表明一种新型冠科菌株可减轻SARS-CoV-2诱导的小鼠肺炎。炎性细胞因子的转录和产生受到抑制,并且冠科菌株适度降低了病毒载量。冠科菌株有潜力成为治疗COVID-19或其他病毒性呼吸道感染的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b0/11619608/f4e57f7fc99b/spectrum.01603-24.f001.jpg

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