Mishchenko E L, V A Ivanisenko V A
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2022 Mar;26(2):121-127. doi: 10.18699/VJGB-22-15.
Coronaviruses (CoVs) belong to the subfamily Orthocoronavirinae of the family Coronaviridae. CoVs are enveloped (+) RNA viruses with unusually long genomes. Severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the novel coronavirus (2019-nCoV, SARS-CoV-2) have been identif ied as causing global pandemics. Clinically tested vaccines are widely used to control rapidly spreading, acute, and often severe infections; however, effective drugs are still not available. The genomes of SARS-CoV-2 and SARS-CoV are approximately 80 % identical, while the genomes of SARS-CoV-2 and MERS-CoV are approximately 50 % identical. This indicates that there may be common mechanisms of coronavirus pathogenesis and, therefore, potential therapeutic targets for each virus may be the same. The enzymes and effector proteins that make up the replication-transcription complex (RTC) of coronaviruses are encoded by a large replicase gene. These enzymes and effector proteins represent promising targets for potential therapeutic drugs. The enzyme targets include papain- and 3C-like cysteine proteinases that process two large viral polyproteins, RNA-dependent RNA polymerase, RNA helicase, viral genome-modifying enzymes, and enzymes with 3'-5' exoribonuclease or uridylate-specif ic endonuclease activity. Currently, there are many studies investigating the complex molecular mechanisms involved in the assembly and function of the RTC. This review will encompass current, modern studies on the properties and complexes of individual non-structural subunits of the RTC, the structures of individual coronavirus RTC subunits, domain organization and functions of subunits, protein-protein interactions, properties and architectures of subunit complexes, the effect of mutations, and the identif ication of mutations affecting the viability of the virus in cell culture. Key words: non-structural proteins CoVs; subunits of replicase CoVs; replication-transcription complex of CoVs; architecture of non-structural protein complexes CoVs.
冠状病毒（CoVs）属于冠状病毒科正冠状病毒亚科。CoVs是具有异常长基因组的包膜（+）RNA病毒。严重急性呼吸综合征冠状病毒（SARS-CoV）、中东呼吸综合征冠状病毒（MERS-CoV）和新型冠状病毒（2019-nCoV，SARS-CoV-2）已被确定为引发全球大流行的病毒。经过临床测试的疫苗被广泛用于控制迅速传播的急性且往往严重的感染；然而，仍然没有有效的药物。SARS-CoV-2和SARS-CoV的基因组约80%相同，而SARS-CoV-2和MERS-CoV的基因组约50%相同。这表明冠状病毒发病机制可能存在共同机制，因此，每种病毒潜在的治疗靶点可能相同。构成冠状病毒复制转录复合体（RTC）的酶和效应蛋白由一个大的复制酶基因编码。这些酶和效应蛋白是潜在治疗药物的有希望的靶点。酶靶点包括处理两种大型病毒多聚蛋白的木瓜蛋白酶样和3C样半胱氨酸蛋白酶、RNA依赖性RNA聚合酶、RNA解旋酶、病毒基因组修饰酶以及具有3'-5'外切核糖核酸酶或尿苷酸特异性内切核酸酶活性的酶。目前，有许多研究在探究RTC组装和功能所涉及的复杂分子机制。本综述将涵盖关于RTC单个非结构亚基的特性和复合体、单个冠状病毒RTC亚基的结构、亚基的结构域组织和功能、蛋白质-蛋白质相互作用、亚基复合体的特性和结构、突变的影响以及影响病毒在细胞培养中生存能力的突变的鉴定等方面的当前现代研究。关键词：冠状病毒非结构蛋白；冠状病毒复制酶亚基；冠状病毒复制转录复合体；冠状病毒非结构蛋白复合体结构
