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Evolutionary Relationships and Sequence-Structure Determinants in Human SARS Coronavirus-2 Spike Proteins for Host Receptor Recognition
ChemRxiv Pub Date : 2020-06-01 , DOI: 10.26434/chemrxiv.12190449
Lalitha Guruprasad

Coronavirus disease 2019 (COVID-19) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). The SARS CoV-2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of CoV and CoV-2 from various host sources in order to analyze the specificity in SARS CoV-2 spike proteins required for causing infection in humans. Our results show that two sequence motifs in the N-terminal domain; "MESEFR" and "SYLTPG" are specific to human SARS CoV-2 and pangolin SARS CoV. In the receptor binding domain (RBD), three sequence loops; VGGNY (loop 1), YQAGSTPC (loop 2), EGFNCY (loop 3) and a tethered disulfide bridge Cys480-Cys488 connecting loops 2 and 3 are structural determinants for the recognition of human ACE-2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, pangolin, human host sources and human SARS CoV-2 identified the bat genome (GenBank code: MN996532.1) and the pangolin SARS CoV genomes as closest to the recent novel human SARS CoV-2 genomes. The bat CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV-2.

中文翻译:

人类SARS冠状病毒2穗蛋白中宿主受体识别的进化关系和序列结构决定因素。

冠状病毒病2019(COVID-19)是由新型严重急性呼吸系统综合症冠状病毒2(SARS CoV-2)引起的大流行性传染病。与SARS CoV相比,SARS CoV-2的传输速度更快,更容易。SARS CoV和SARS CoV-2都通过其糖基化的突突蛋白识别人血管紧张素转化酶2(ACE-2)受体。我们分析了来自不同宿主来源的CoV和CoV-2代表性刺突蛋白的多重序列比对和系统树,以分析引起人类感染所需的SARS CoV-2刺突蛋白的特异性。我们的结果表明,在N末端域中有两个序列基序。“ MESEFR”和“ SYLTPG”特异于人SARS CoV-2和穿山甲SARS CoV。在受体结合结构域(RBD)中,有三个序列环。VGGNY(回路1),YQAGSTPC(回路2),EGFNCY(回路3)和连接回路2和3的束缚二硫键Cys480-Cys488是识别人ACE-2受体的结构决定因素。对来自蝙蝠,灵猫,穿山甲,人类宿主和人类SARS CoV-2的代表性SARS CoV的完整基因组分析确定了蝙蝠基因组(GenBank代码:MN996532.1)和穿山甲SARS CoV基因组与最近的新型人类SARS最接近CoV-2基因组。蝙蝠冠状病毒基因组(GenBank代码:MG772933和MG772934)是在诱变发展成为人类SARS CoV-2的进化中间产物。人类宿主来源和人类SARS CoV-2鉴定出蝙蝠基因组(GenBank代码:MN996532.1)和穿山甲SARS CoV基因组与最近的新型人类SARS CoV-2基因组最接近。蝙蝠冠状病毒基因组(GenBank代码:MG772933和MG772934)是在诱变发展成为人类SARS CoV-2的进化中间产物。人类宿主来源和人类SARS CoV-2鉴定出蝙蝠基因组(GenBank代码:MN996532.1)和穿山甲SARS CoV基因组与最近的新型人类SARS CoV-2基因组最接近。蝙蝠冠状病毒基因组(GenBank代码:MG772933和MG772934)是在诱变发展成为人类SARS CoV-2的进化中间产物。
更新日期:2020-06-01
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