Fig. 1: Structure, genome and life cycle of SARS-CoV-2.

a | Coronaviruses form an enveloped spherical particle that consists of four structural proteins (spike (S), envelope (E), membrane (M) and nucleocapsid (N)) and a positive-sense, single-stranded RNA (ssRNA) genome that is 30 kb in length. b | The 5′-terminal two-thirds of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes polyproteins pp1a and pp1ab, which are cleaved into 16 different non-structural proteins. Structural proteins are encoded in the 3′-terminal one-third of the genome. The S protein consists of two subunits; the S1 subunit contains a receptor-binding domain (RBD) that binds to angiotensin-converting enzyme 2 (ACE2) on the surface of host cells, whereas the S2 subunit mediates fusion between the membranes of the virus and the host cell. Compared with the S protein of SARS-CoV, the S protein of SARS-CoV-2 has two notable features. First, within the RBD of the S1 subunit, five of the six residues that are crucial for binding to human ACE2 are mutated. Second, an insertion of four amino acid residues at the boundary between the S1 and S2 subunits is present in SARS-CoV-2 but not in SARS-CoV, which introduces a novel furin cleavage site. c | SARS-CoV-2 infection is triggered by the binding of the S protein to ACE2 on the surface of host cells, and the viral complex is incorporated into the cytoplasm either by direct fusion with the cell membrane or via endocytosis with later release into the cytoplasm from the endocytic vesicle. The S protein is cleaved at the S1/S2 boundary and the S2 subunit facilitates membrane fusion. The viral genome RNA is released into the cytoplasm, and the first open reading frame (ORF) is translated into polyproteins pp1a and pp1ab, which are then cleaved by viral proteases into small, non-structural proteins such as RNA-dependent RNA polymerase (RdRP). The viral genomic RNA is replicated by RdRP. Viral nucleocapsids are assembled from genomic RNA and N proteins in the cytoplasm, whereas budding of new particles occurs at the membrane of the endoplasmic reticulum (ER)–Golgi intermediate compartment. Finally, the genomic RNA and structural proteins are assembled into new viral particles, leading to their release via exocytosis. 3CL, 3-chymotrypsin-like protease.