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有证据表明,山槐种子凝集素(MASL)对口腔鳞状细胞具有多效性作用,可抑制SARS-CoV-2感染和新冠肺炎疾病进展。

Evidence that Maackia amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells to inhibit SARS-CoV-2 infection and COVID-19 disease progression.

作者信息

Sheehan Stephanie A, Hamilton Kelly L, Retzbach Edward P, Balachandran Premalatha, Krishnan Harini, Leone Paola, Goldberg Gary S

机构信息

Department of Molecular Biology, and Graduate School of Biomedical Sciences, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA.

National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, MS 38677, USA.

出版信息

Res Sq. 2020 Oct 23:rs.3.rs-93851. doi: 10.21203/rs.3.rs-93851/v1.

Abstract

COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 23 million confirmed COVID-19 cases that have cause over 800 thousand deaths worldwide as of August 19th, 2020. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.

摘要

2020年1月,新型冠状病毒肺炎(COVID-19)被宣布为国际突发公共卫生事件,并于3月成为大流行病。截至2020年8月19日,全球确诊的COVID-19病例超过2300万例,导致超过80万人死亡。COVID-19由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒引起。SARS-CoV-2呈现一种表面“刺突”蛋白,该蛋白与血管紧张素转换酶2(ACE2)受体结合以感染宿主细胞。除呼吸道外,SARS-CoV-2还可感染口腔黏膜细胞,这些细胞也表达ACE2受体。刺突蛋白和ACE2蛋白高度糖基化,并带有指导病毒与宿主相互作用及感染的唾液酸修饰。龙牙楤木种子凝集素(MASL)对唾液酸修饰的蛋白具有很强的亲和力,可作为抗病毒剂。在此,我们报告MASL靶向ACE2受体,降低ACE2表达和糖基化,抑制SARS-CoV-2刺突蛋白的结合,并降低导致COVID-19患者急性呼吸窘迫综合征(ARDS)的口腔上皮细胞炎性介质的表达。这项工作确定MASL为一种有潜力抑制SARS-CoV-2感染和与COVID-19相关的炎性综合征的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8f5/7587785/2c50e03e9e7c/nihpp-rs93851v1-f0001.jpg

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