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解析 SARS-CoV-2 受体结合基序的进化。

Untangling the Evolution of the Receptor-Binding Motif of SARS-CoV-2.

机构信息

Departamento de Ingeniería Genética, Cinvestav Unidad Irapuato, Km 9.6 Libramiento Norte Carretera Irapuato-León, C.P. 36824, Irapuato, Gto., Mexico.

出版信息

J Mol Evol. 2024 Jun;92(3):329-337. doi: 10.1007/s00239-024-10175-y. Epub 2024 May 22.

Abstract

The spike protein determines the host-range specificity of coronaviruses. In particular, the Receptor-Binding Motif in the spike protein from SARS-CoV-2 contains the amino acids involved in molecular recognition of the host Angiotensin Converting Enzyme 2. Therefore, to understand how SARS-CoV-2 acquired its capacity to infect humans it is necessary to reconstruct the evolution of this important motif. Early during the pandemic, it was proposed that the SARS-CoV-2 Receptor-Binding Domain was acquired via recombination with a pangolin infecting coronavirus. This proposal was challenged by an alternative explanation that suggested that the Receptor-Binding Domain from SARS-CoV-2 did not originated via recombination with a coronavirus from a pangolin. Instead, this alternative hypothesis proposed that the Receptor-Binding Motif from the bat coronavirus RaTG13, was acquired via recombination with an unidentified coronavirus. And as a consequence of this event, the Receptor-Binding Domain from the pangolin coronavirus appeared as phylogenetically closer to SARS-CoV-2. Recently, the genomes from coronaviruses from Cambodia (bat_RShST182/200) and Laos (BANAL-20-52/103/247) which are closely related to SARS-CoV-2 were reported. However, no detailed analysis of the evolution of the Receptor-Binding Motif from these coronaviruses was reported. Here we revisit the evolution of the Receptor-Binding Domain and Motif in the light of the novel coronavirus genome sequences. Specifically, we wanted to test whether the above coronaviruses from Cambodia and Laos were the source of the Receptor-Binding Domain from RaTG13. We found that the Receptor-Binding Motif from these coronaviruses is phylogenetically closer to SARS-CoV-2 than to RaTG13. Therefore, the source of the Receptor-Binding Domain from RaTG13 is still unidentified. In accordance with previous studies, our results are consistent with the hypothesis that the Receptor-Binding Motif from SARS-CoV-2 evolved by vertical inheritance from a bat-infecting population of coronaviruses.

摘要

刺突蛋白决定了冠状病毒的宿主范围特异性。特别是,SARS-CoV-2 刺突蛋白中的受体结合基序包含了与宿主血管紧张素转换酶 2 分子识别相关的氨基酸。因此,要了解 SARS-CoV-2 是如何获得感染人类的能力,就有必要重建这个重要基序的进化过程。在大流行早期,有人提出,SARS-CoV-2 的受体结合结构域是通过与感染穿山甲的冠状病毒重组获得的。这一说法受到了另一种解释的挑战,该解释表明,SARS-CoV-2 的受体结合结构域并非通过与穿山甲冠状病毒重组产生。相反,这个替代假说提出,蝙蝠冠状病毒 RaTG13 的受体结合基序是通过与一种未识别的冠状病毒重组获得的。因此,由于这一事件的发生,穿山甲冠状病毒的受体结合结构域在系统发育上与 SARS-CoV-2 更为接近。最近,报道了与 SARS-CoV-2 密切相关的柬埔寨(bat_RShST182/200)和老挝(BANAL-20-52/103/247)冠状病毒的基因组。然而,这些冠状病毒的受体结合基序的进化没有得到详细分析。在这里,我们根据新型冠状病毒基因组序列重新审视受体结合结构域和基序的进化。具体来说,我们想测试柬埔寨和老挝的上述冠状病毒是否是 RaTG13 的受体结合结构域的来源。我们发现,这些冠状病毒的受体结合基序在系统发育上与 SARS-CoV-2 比与 RaTG13 更为接近。因此,RaTG13 的受体结合结构域的来源仍然未知。与之前的研究一致,我们的结果与受体结合基序从蝙蝠冠状病毒垂直遗传进化的假说一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/159b/11168982/71b8e5395bbe/239_2024_10175_Fig1_HTML.jpg

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