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Can Neurotropic Free-Living Amoeba Serve as a Model to Study SARS-CoV-2 Pathogenesis?
ACS Chemical Neuroscience ( IF 5 ) Pub Date : 2020-10-29 , DOI: 10.1021/acschemneuro.0c00653
Abdul Mannan Baig 1
Affiliation  

Of the single-celled eukaryotic microbes, Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba spp. are known to cause fatal encephalitis in humans. Being eukaryotes, these cells have been used as a model for studying and understanding complex cellular processes in humans like cell motility, phagocytosis, and metabolism. The ongoing pandemic caused by SARS-CoV-2 that infects multiple organs has emerged as a challenge to unravel its mode of infection and the pathogenicity resulting in eukaryotic cell death. Working with these single-celled eukaryotic microbes provided us the opportunity to plan bioinformatic approaches to look into the likelihood of studying the known and alternative mode of infection of the SARS-CoV-2 in eukaryotic cells. Genome databases of N. fowleri, B. mandrillaris, and Acanthamoeba spp. were used to explore the expression of angiotensin-converting enzyme 2 (ACE2), androgen-regulated serine protease precursor (TMPRSS2), CD4, CD147, and furin that are known to be cardinal for SARS-CoV-2 in recognition and binding to human cells. It was hypothesized that if a receptor-dependent or phagocytosis-assisted SARS-CoV-2 uptake does occur in free-living amoebae (FLA), this model can provide an alternative to human cells to study cellular recognition and binding of SARS-CoV-2 that can help design drugs and treatment modalities in COVID-19. We show that, of the FLA, ACE2 and TMPRSS2 are not expressed in Acanthamoeba spp. and B. mandrillaris, but primitive forms of these cell recognition proteins were seen to be encoded in N. fowleri. Acanthamoeba spp. and N. fowleri encode for human-like furin which is a known SARS-CoV-2 spike protein involved in host cell recognition and binding.

中文翻译:

嗜神经性自由变形虫可以作为研究SARS-CoV-2发病机理的模型吗?

在单细胞真核微生物中,Naegleria fowleriBalamuthia mandrillaris棘阿米巴spp。已知会导致人类致命的脑炎。这些细胞是真核生物,已被用作研究和理解人类复杂细胞过程(例如细胞运动,吞噬作用和新陈代谢)的模型。由SARS-CoV-2感染多个器官引起的持续大流行已经成为挑战,以揭示其感染方式和致病性,导致真核细胞死亡。与这些单细胞真核微生物的合作为我们提供了计划生物信息学方法的机会,以研究研究真核细胞中SARS-CoV-2的已知和替代感染模式的可能性。N. fowleriB。mandrillarisAcanthamoeba的基因组数据库spp。用于研究血管紧张素转化酶2(ACE2),雄激素调节的丝氨酸蛋白酶前体(TMPRSS2),CD4,CD147和弗林蛋白酶的表达,这些蛋白已知是SARS-CoV-2的主要识别和结合人细胞。假设如果在自由生活的变形虫(FLA)中确实发生了受体依赖性或吞噬作用辅助的SARS-CoV-2吸收,则该模型可以为人类细胞提供替代方案,以研究细胞对SARS-CoV-的识别和结合2可以帮助设计COVID-19中的药物和治疗方式。我们表明,在FLA中,ACE2和TMPRSS2在棘阿米巴属菌种中不表达。和B. mandrillaris,但是这些细胞识别蛋白的原始形式被认为在福勒猪笼草中编码。棘阿米巴spp。FowleriN. fowleri编码人样弗林蛋白酶,这是一种已知的SARS-CoV-2刺突蛋白,参与宿主细胞的识别和结合。
更新日期:2020-11-18
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