SARS-CoV-2 is an extremely contagious respiratory virus causing adult atypical pneumonia COVID-19 with severe acute respiratory syndrome (SARS). SARS-CoV-2 has a single-stranded, positive-sense RNA (+RNA) genome of ~ 29.9 kb and exhibits significant genetic shift from different isolates. After entering the susceptible cells expressing both ACE2 and TMPRSS2, the SARS-CoV-2 genome directly functions as an mRNA to translate two polyproteins from the ORF1a and ORF1b region, which are cleaved by two viral proteases into sixteen non-structural proteins (nsp1-16) to initiate viral genome replication and transcription. The SARS-CoV-2 genome also encodes four structural (S, E, M and N) and up to six accessory (3a, 6, 7a, 7b, 8, and 9b) proteins, but their translation requires newly synthesized individual subgenomic RNAs (sgRNA) in the infected cells. Synthesis of the full-length viral genomic RNA (gRNA) and sgRNAs are conducted inside double-membrane vesicles (DMVs) by the viral replication and transcription complex (RTC), which comprises nsp7, nsp8, nsp9, nsp12, nsp13 and a short RNA primer. To produce sgRNAs, RTC starts RNA synthesis from the highly structured gRNA 3' end and switches template at various transcription regulatory sequence (TRSB) sites along the gRNA body probably mediated by a long-distance RNA–RNA interaction. The TRS motif in the gRNA 5' leader (TRSL) is responsible for the RNA–RNA interaction with the TRSB upstream of each ORF and skipping of the viral genome in between them to produce individual sgRNAs. Abundance of individual sgRNAs and viral gRNA synthesized in the infected cells depend on the location and read-through efficiency of each TRSB. Although more studies are needed, the unprecedented COVID-19 pandemic has taught the world a painful lesson that is to invest and proactively prepare future emergence of other types of coronaviruses and any other possible biological horrors.

中文翻译：

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SARS-CoV-2：从发现到基因组结构、转录和复制

SARS-CoV-2 是一种传染性极强的呼吸道病毒，可导致成人非典型肺炎 COVID-19 伴严重急性呼吸系统综合症 (SARS)。SARS-CoV-2 具有约 29.9 kb 的单链正链 RNA (+RNA) 基因组，并且表现出来自不同分离株的显着遗传转变。在进入表达 ACE2 和 TMPRSS2 的易感细胞后，SARS-CoV-2 基因组直接作为 mRNA 将 ORF1a 和 ORF1b 区域的两种多聚蛋白翻译成 16 种非结构蛋白（nsp1- 16) 启动病毒基因组复制和转录。SARS-CoV-2 基因组还编码四种结构蛋白（S、E、M 和 N）和多达六种辅助蛋白（3a、6、7a、7b、8 和 9b），但它们的翻译需要新合成的单个亚基因组 RNA (sgRNA) 在受感染的细胞中。全长病毒基因组 RNA (gRNA) 和 sgRNA 的合成通过病毒复制和转录复合物 (RTC) 在双膜囊泡 (DMV) 内进行，RTC 包括 nsp7、nsp8、nsp9、nsp12、nsp13 和一个短 RNA底漆。为了产生 sgRNA，RTC 从高度结构化的 gRNA 3' 末端开始 RNA 合成，并在可能由长距离 RNA-RNA 相互作用介导的 gRNA 主体的各种转录调控序列 (TRSB) 位点切换模板。gRNA 5' 前导 (TRSL) 中的 TRS 基序负责 RNA-RNA 与每个 ORF 上游的 TRSB 相互作用，并跳过它们之间的病毒基因组以产生单个 sgRNA。在受感染细胞中合成的单个 sgRNA 和病毒 gRNA 的丰度取决于每个 TRSB 的位置和通读效率。