Fig. 1.

Fig. 1. Replication of coronaviruses. The coronavirus is an enveloped virus with a positive sense, single-stranded RNA genome, which is encapsidated by nucleocapsid (N) protein. Its virion consists of spike (S), envelope (E), membrane (M), and N proteins. The entry of coronaviruses is mediated either by clathrin-mediated endocytosis or by membrane fusion facilitated by their receptors: ACE2, TMPRSS2, and cathepsin B/L (①). The released viral genome (②) is translated generating viral polyprotein pp1a and pp1ab from two open reading frames (③); ORF1a and ORF1b, which encode non-structural protein (nsp) complexes 1-11 and nsp12-16, respectively. The pp1a and pp1ab are then processed into individual nsps including replicase proteins (④). The replicase proteins establish replication and transcription complex (RTC) to initiate the synthesis of a negative-strand (-) to synthesize a new positive-strand RNA genome (⑤). During replication, subgenomic RNAs (sgRNAs) are generated, which encode structural and accessory proteins (⑥). The translated structural proteins migrate to the endoplasmic reticulum (ER) and Golgi apparatus membranes (⑦), where the viral virion is assembled with the encapsidated genomic RNAs (⑧). Finally, the progeny virions are released from the host cell by exocytosis (⑨, ⑩). Of note, the S1-S2 boundary region of S protein in SARS-CoV-2 and MERS-CoV is cleaved by furin during virion maturation before the release of progeny virions, whereas SARS-CoV remains in an unprocessed form.

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