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一种强效的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)中和人单克隆抗体,可降低叙利亚仓鼠的病毒载量和疾病严重程度。

A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters.

作者信息

Fagre Anna C, Manhard John, Adams Rachel, Eckley Miles, Zhan Shijun, Lewis Juliette, Rocha Savannah M, Woods Catherine, Kuo Karina, Liao Wuxiang, Li Lin, Corper Adam, Challa Dilip, Mount Emily, Tumanut Christine, Tjalkens Ronald B, Aboelleil Tawfik, Fan Xiaomin, Schountz Tony

出版信息

bioRxiv. 2020 Sep 28:2020.09.25.313601. doi: 10.1101/2020.09.25.313601.

Abstract

The emergence of COVID-19 has led to a pandemic that has caused millions of cases of disease, variable morbidity and hundreds of thousands of deaths. Currently, only remdesivir and dexamethasone have demonstrated limited efficacy, only slightly reducing disease burden, thus novel approaches for clinical management of COVID-19 are needed. We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus . Administration of the lead antibody clone to Syrian hamsters challenged with SARS-CoV-2 significantly reduced viral load and histopathology score in the lungs. Moreover, the antibody interrupted monocyte infiltration into the lungs, which may have contributed to the reduction of disease severity by limiting immunopathological exacerbation. The use of this antibody could provide an important therapy for treatment of COVID-19 patients.

摘要

新型冠状病毒肺炎(COVID-19)的出现引发了一场大流行,导致数百万病例、不同程度的发病率以及数十万人死亡。目前,只有瑞德西韦和地塞米松显示出有限的疗效,仅略微减轻了疾病负担,因此需要针对COVID-19临床管理的新方法。我们从酵母展示文库中鉴定出一组对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白受体结合域具有特异性的人单克隆抗体克隆,这些克隆可中和该病毒。将先导抗体克隆给予感染SARS-CoV-2的叙利亚仓鼠后,显著降低了肺部的病毒载量和组织病理学评分。此外,该抗体阻断了单核细胞向肺部的浸润,这可能通过限制免疫病理加重而有助于减轻疾病严重程度。使用这种抗体可为COVID-19患者的治疗提供一种重要的疗法。

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