Fig. 2.

Replication cycle of HCoV. The virus enters the host cell by binding protein S to the ACE2 receptor (SARS-CoV and SARS-CoV-2) or the DPP4 receptor (MERS-CoV), leading the viral membrane fusion with the cell membrane host (1). Fusion occurs because of S protein cleavage, allowing entry through the endosomal pathway (2). The viral RNA is released into the cell cytoplasm (3) and the pp1a and pp1ab polyproteins (4) are translated, which will be cleaved by the proteases of the RTC complex (5), synthesizing the (+) and (−) RNAs (6). From (−) gRNA, sgRNAs will be discontinuously transcribed until act as mRNAs (7) and finally being translated into the structural proteins (8) that will be transferred to the ERGIC intermediate complex (9). The N proteins then bind to the (+) gRNA in the cytoplasm and are assembled with structural proteins in the ERGIC complex (10). Vesicles containing virion are transported to the plasma membrane and released via exocytosis (11) in the extracellular space, thus infecting neighboring cells.