Gorkhali Ritesh, Koirala Prashanna, Rijal Sadikshya, Mainali Ashmita, Baral Adesh, Bhattarai Hitesh Kumar
Department of Biotechnology, Kathmandu University, Dhulikhel, Nepal.
Bioinform Biol Insights. 2021 Jun 22;15:11779322211025876. doi: 10.1177/11779322211025876. eCollection 2021.
SARS-CoV-2 virus, the causative agent of COVID-19 pandemic, has a genomic organization consisting of 16 nonstructural proteins (nsps), 4 structural proteins, and 9 accessory proteins. Relative of SARS-CoV-2, SARS-CoV, has genomic organization, which is very similar. In this article, the function and structure of the proteins of SARS-CoV-2 and SARS-CoV are described in great detail. The nsps are expressed as a single or two polyproteins, which are then cleaved into individual proteins using two proteases of the virus, a chymotrypsin-like protease and a papain-like protease. The released proteins serve as centers of virus replication and transcription. Some of these nsps modulate the host's translation and immune systems, while others help the virus evade the host immune system. Some of the nsps help form replication-transcription complex at double-membrane vesicles. Others, including one RNA-dependent RNA polymerase and one exonuclease, help in the polymerization of newly synthesized RNA of the virus and help minimize the mutation rate by proofreading. After synthesis of the viral RNA, it gets capped. The capping consists of adding GMP and a methylation mark, called cap 0 and additionally adding a methyl group to the terminal ribose called cap1. Capping is accomplished with the help of a helicase, which also helps remove a phosphate, two methyltransferases, and a scaffolding factor. Among the structural proteins, S protein forms the receptor of the virus, which latches on the angiotensin-converting enzyme 2 receptor of the host and N protein binds and protects the genomic RNA of the virus. The accessory proteins found in these viruses are small proteins with immune modulatory roles. Besides functions of these proteins, solved X-ray and cryogenic electron microscopy structures related to the function of the proteins along with comparisons to other coronavirus homologs have been described in the article. Finally, the rate of mutation of SARS-CoV-2 residues of the proteome during the 2020 pandemic has been described. Some proteins are mutated more often than other proteins, but the significance of these mutation rates is not fully understood.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒是新冠疫情的病原体,其基因组结构由16种非结构蛋白(nsps)、4种结构蛋白和9种辅助蛋白组成。SARS-CoV-2的近亲SARS-CoV,其基因组结构与之非常相似。在本文中,详细描述了SARS-CoV-2和SARS-CoV蛋白质的功能和结构。nsps以单个或两个多蛋白的形式表达,然后利用病毒的两种蛋白酶,即类胰凝乳蛋白酶和类木瓜蛋白酶,将其切割成单个蛋白质。释放出的蛋白质作为病毒复制和转录的中心。其中一些nsps调节宿主的翻译和免疫系统,而其他nsps则帮助病毒逃避免疫系统。一些nsps有助于在双膜囊泡处形成复制转录复合体。其他nsps,包括一种RNA依赖性RNA聚合酶和一种核酸外切酶,有助于病毒新合成RNA的聚合,并通过校对帮助将突变率降至最低。病毒RNA合成后会进行加帽。加帽包括添加GMP和一个甲基化标记,称为帽0,另外在末端核糖上添加一个甲基,称为帽1。加帽是在一种解旋酶的帮助下完成的,该解旋酶还帮助去除一个磷酸基团、两种甲基转移酶和一个支架因子。在结构蛋白中,S蛋白形成病毒的受体,它锁定在宿主的血管紧张素转换酶2受体上;N蛋白结合并保护病毒的基因组RNA。这些病毒中的辅助蛋白是具有免疫调节作用的小蛋白。除了这些蛋白质的功能外,本文还描述了与蛋白质功能相关的已解析的X射线和低温电子显微镜结构,以及与其他冠状病毒同源物的比较。最后,描述了2020年疫情期间SARS-CoV-2蛋白质组残基的突变率。一些蛋白质比其他蛋白质更容易发生突变,但这些突变率的意义尚未完全明了。
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