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 ). 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.
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