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SARS-CoV-2,引发此次大流行的冠状病毒:分子与结构视角

SARS-CoV-2, the pandemic coronavirus: Molecular and structural insights.

机构信息

Department of Botany, Savitribai Phule Pune University, Pune, India.

Department of Microbiology, Savitribai Phule Pune University, Pune, India.

出版信息

J Basic Microbiol. 2021 Mar;61(3):180-202. doi: 10.1002/jobm.202000537. Epub 2021 Jan 18.

Abstract

The outbreak of a novel coronavirus associated with acute respiratory disease, called COVID-19, marked the introduction of the third spillover of an animal coronavirus (CoV) to humans in the last two decades. The genome analysis with various bioinformatics tools revealed that the causative pathogen (SARS-CoV-2) belongs to the subgenus Sarbecovirus of the genus Betacoronavirus, with highly similar genome as bat coronavirus and receptor-binding domain (RBD) of spike glycoprotein as Malayan pangolin coronavirus. Based on its genetic proximity, SARS-CoV-2 is likely to have originated from bat-derived CoV and transmitted to humans via an unknown intermediate mammalian host, probably Malayan pangolin. Further, spike protein S1/S2 cleavage site of SARS-CoV-2 has acquired polybasic furin cleavage site which is absent in bat and pangolin suggesting natural selection either in an animal host before zoonotic transfer or in humans following zoonotic transfer. In the current review, we recapitulate a preliminary opinion about the disease, origin and life cycle of SARS-CoV-2, roles of virus proteins in pathogenesis, commonalities, and differences between different corona viruses. Moreover, the crystal structures of SARS-CoV-2 proteins with unique characteristics differentiating it from other CoVs are discussed. Our review also provides comprehensive information on the molecular aspects of SARS-CoV-2 including secondary structures in the genome and protein-protein interactions which can be useful to understand the aggressive spread of the SARS-CoV-2. The mutations and the haplotypes reported in the SARS-CoV-2 genome are summarized to understand the virus evolution.

摘要

一种新型冠状病毒引发的急性呼吸道疾病爆发,被称为 COVID-19,标志着在过去二十年中,第三种动物冠状病毒(CoV)溢出到人类。通过各种生物信息学工具进行的基因组分析表明,病原体(SARS-CoV-2)属于贝塔冠状病毒属的Sarbecovirus 亚属,其基因组与蝙蝠冠状病毒高度相似,刺突糖蛋白的受体结合域(RBD)与马来穿山甲冠状病毒相似。基于其遗传关系,SARS-CoV-2 可能源自蝙蝠衍生的 CoV,并通过未知的中间哺乳动物宿主(可能是马来穿山甲)传播给人类。此外,SARS-CoV-2 的刺突蛋白 S1/S2 切割位点获得了多碱性弗林切割位点,而蝙蝠和穿山甲中不存在该位点,这表明在人畜共患病转移前的动物宿主中或在人畜共患病转移后的人类中发生了自然选择。在本综述中,我们总结了对 SARS-CoV-2 的疾病、起源和生命周期、病毒蛋白在发病机制中的作用、不同冠状病毒之间的共同性和差异性的初步看法。此外,还讨论了具有独特特征的 SARS-CoV-2 蛋白的晶体结构,这些特征使其与其他 CoV 区分开来。我们的综述还提供了 SARS-CoV-2 的分子方面的全面信息,包括基因组和蛋白-蛋白相互作用中的二级结构,这有助于理解 SARS-CoV-2 的攻击性传播。还总结了 SARS-CoV-2 基因组中报告的突变和单倍型,以了解病毒的进化。

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