key: cord-0885317-5dqrhssw authors: Chen, Yu; Liu, Qianyun; Guo, Deyin title: Emerging coronaviruses: Genome structure, replication, and pathogenesis date: 2020-02-07 journal: J Med Virol DOI: 10.1002/jmv.25681 sha: 0d25da69e0253800ace69148c784b52997720469 doc_id: 885317 cord_uid: 5dqrhssw The recent emergence of a novel coronavirus (2019‐nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats. CoVs belong to the subfamily Coronavirinae in the family of Coronaviridae of the order Nidovirales, and this subfamily includes four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus ( Figure 1A ). The genome of CoVs is a single-stranded positive-sense RNA (+ssRNA) (~30 kb) with 5′-cap structure and 3′-poly-A tail. The genomic RNA is used as template to directly translate polyprotein 1a/1ab (pp1a/pp1ab), which encodes nonstructural proteins (nsps) to form the replication-transcription complex (RTC) in a double-membrane vesicles (DMVs). 6 Subsequently, a nested set of subgenomic RNAs (sgRNAs) are synthesized by RTC in a manner of discontinuous transcription. 7 These subgenomic messenger RNAs (mRNAs) possess common 5′-leader and 3′-terminal sequences. Transcription termination and subsequent acquisition of a leader RNA occurs at transcription regulatory sequences, located between open reading frames (ORFs). These minus-strand sgRNAs serve as the templates for the production of subgenomic mRNAs. 8, 9 The genome and subgenomes of a typical CoV contain at least six ORFs. The first ORFs (ORF1a/b), about two-thirds of the whole genome length, encode 16 nsps (nsp1-16), except Gammacoronavirus that lacks nsp1. There is a −1 frameshift between ORF1a and ORF1b, leading to production of two polypeptides: pp1a and pp1ab. These polypeptides are processed by virally encoded chymotrypsin-like protease (3CL pro ) or main protease (M pro ) and one or two papain-like protease into 16 nsps. 10, 11 Other ORFs on the one-third of the genome near the 3′- Table 1 . CoVs can infect livestock, birds, bats, mice, whales, and many other wild animals, and they can cause great economic loss. For example, in 2016, an HKU2-related bat CoV, swine acute diarrhea syndrome CoV, caused a large-scale outbreak of fatal disease in pigs in Southern China, and more than 24 000 piglets were dead. 62 This is the first documented spillover of a bat CoV that caused severe disease in livestock. 4, 63 The new CoV, 2019-nCoV, which belongs to betacoronaviruses based on sequence analysis ( Figure 1A) , can also infect the lower respiratory tract and cause pneumonia in human, but it seems that the symptoms are milder than SARS and MERS. Up to 20 January Table 2 for better understanding the pathogenesis of CoVs. 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