All the structural and accessory proteins are translated from the sgRNAs of CoVs. Besides these four main structural proteins, different CoVs encode special structural and accessory proteins, such as HE protein, 3a/b protein, and 4a/b protein (Figure 1B, lower panel). Other ORFs on the one‐third of the genome near the 3′‐terminus encodes at least four main structural proteins: spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins. 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. There is a −1 frameshift between ORF1a and ORF1b, leading to production of two polypeptides: pp1a and pp1ab. The first ORFs (ORF1a/b), about two‐thirds of the whole genome length, encode 16 nsps (nsp1‐16), except Gammacoronavirus that lacks nsp1. The genome and subgenomes of a typical CoV contain at least six ORFs. Viral names: HKU, coronaviruses identified by Hong Kong University HCoV, human coronavirus IBV, infectious bronchitis virus MHV, murine hepatitis virus TGEV, transmissible gastroenteritis virus 2019‐nCoV, 2019 novel coronavirus CoVs, coronavirus HE, hemagglutinin‐esterase. S, E, M, and N indicate the four structural proteins spike, envelope, membrane, and nucleocapsid.
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Pp1a and pp1b represent the two long polypeptides that are processed into 16 nonstructural proteins. B, The genome structure of four genera of coronaviruses. A, The phylogenetic tree of representative CoVs, with the new coronavirus 2019‐nCoV highlighted in red. The genomic structure and phylogenetic tree of coronaviruses.
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These minus‐strand sgRNAs serve as the templates for the production of subgenomic mRNAs. Transcription termination and subsequent acquisition of a leader RNA occurs at transcription regulatory sequences, located between open reading frames (ORFs). These subgenomic messenger RNAs (mRNAs) possess common 5′‐leader and 3′‐terminal sequences. Subsequently, a nested set of subgenomic RNAs (sgRNAs) are synthesized by RTC in a manner of discontinuous transcription. 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). The genome of CoVs is a single‐stranded positive‐sense RNA (+ssRNA) (~30 kb) with 5′‐cap structure and 3′‐poly‐A tail. Thus, there is an urgent need to develop effective therapies and vaccines against CoVs.Ģ. CORONAVIRAL GENOME STRUCTURE AND REPLICATIONĬoVs 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). It is highly likely that new CoV outbreaks are unavoidable in the future due to changes of the climate and ecology, and the increased interactions of human with animals. The sporadic emergence and outbreaks of new types of CoVs remind us that CoVs are a severe global health threat. On 12 January 2020, the World Health Organization temporarily named the new virus as 2019 novel coronavirus (2019‐nCoV). The causative agent of the mystery pneumonia has been identified as a novel coronavirus (nCoV) by deep sequencing and etiological investigations by at least five independent laboratories of China ( and ).
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Chinese government and researchers have been taking swift measures to control the outbreak and conduct the etiological studies. The outbreaks of the severe acute respiratory syndrome (SARS) in 2002/2003 and the Middle East respiratory syndrome (MERS) in 2012 have demonstrated the possibility of animal‐to‐human and human‐to‐human transmission of newly emerging CoVs.Īn outbreak of mystery pneumonia in Wuhan since December 2019 has been drawing tremendous attention around the world. They can infect respiratory, gastrointestinal, hepatic, and central nervous system of human, livestock, birds, bat, mouse, and many other wild animals. Coronaviruses (CoVs) are important pathogens for human and vertebrates.