Although the cleavage site of SARS-CoV is known, that of SARS-CoV-2 S has not yet been reported. Similar to other coronaviruses, the S protein of SARS-CoV-2 is cleaved into S1 and S2 subunits by cellular proteases, and the serine protease TMPRSS2 is used as a protein primer. During viral infection, target cell proteases activate the S protein by cleaving it into S1 and S2 subunits, which is necessary for activating the membrane fusion domain after viral entry into target cells. In the native state, the CoV S protein exists as an inactive precursor. The structure of the SARS-CoV-2 trimeric S protein has been determined by cryo-electron microscopy at the atomic level, revealing different conformations of the S RBD domain in opened and closed states and its corresponding functions (Fig. Based on the structure of coronavirus S protein monomers, the S1 and S2 subunits form the bulbous head and stalk region. S protein trimers visually form a characteristic bulbous, crown-like halo surrounding the viral particle (Fig. In the S1 subunit, there is an N-terminal domain (14–305 residues) and a receptor-binding domain (RBD, 319–541 residues) the fusion peptide (FP) (788–806 residues), heptapeptide repeat sequence 1 (HR1) (912–984 residues), HR2 (1163–1213 residues), TM domain (1213–1237 residues), and cytoplasm domain (1237–1273 residues) comprise the S2 subunit (Fig. The total length of SARS-CoV-2 S is 1273 aa and consists of a signal peptide (amino acids 1–13) located at the N-terminus, the S1 subunit (14–685 residues), and the S2 subunit (686–1273 residues) the last two regions are responsible for receptor binding and membrane fusion, respectively. The spikes are coated with polysaccharide molecules to camouflage them, evading surveillance of the host immune system during entry. S normally exists in a metastable, prefusion conformation once the virus interacts with the host cell, extensive structural rearrangement of the S protein occurs, allowing the virus to fuse with the host cell membrane. With a size of 180–200 kDa, the S protein consists of an extracellular N-terminus, a transmembrane (TM) domain anchored in the viral membrane, and a short intracellular C-terminal segment. Viral RNA is replicated, and structural proteins are synthesized, assembled, and packaged in the host cell, after which viral particles are released (Fig. Once the virus enters the cell, the viral RNA is released, polyproteins are translated from the RNA genome, and replication and transcription of the viral RNA genome occur via protein cleavage and assembly of the replicase–transcriptase complex. When the S protein binds to the receptor, TM protease serine 2 (TMPRSS2), a type 2 TM serine protease located on the host cell membrane, promotes virus entry into the cell by activating the S protein. Ī large number of glycosylated S proteins cover the surface of SARS-CoV-2 and bind to the host cell receptor angiotensin-converting enzyme 2 (ACE2), mediating viral cell entry. The S, E, M, and N genes encode structural proteins, whereas nonstructural proteins, such as 3-chymotrypsin-like protease, papain-like protease, and RNA-dependent RNA polymerase, are encoded by the ORF region. Gene fragments express structural and nonstructural proteins. An RNA-based metagenomic next-generation sequencing approach has been applied to characterize its entire genome, which is 29,881 bp in length (GenBank no. SARS-CoV-2 is a single-stranded RNA-enveloped virus. As the epidemic spreads, it is critical to find a specific therapeutic for COVID-19, and vaccines targeting various SARS-CoV-2 proteins are under development. Conversely, the other three, SARS-CoV, MERS-CoV, and SARS-CoV-2, are able to cause severe symptoms and even death, with fatality rates of 10%, 37%, and 5%, respectively.Īlthough a large number of studies and clinical trials are being launched on COVID-19 around the world, no evidence from randomized clinical trials has shown that any potential therapy improves outcomes in patients. It is the seventh known coronavirus to infect humans four of these coronaviruses (229E, NL63, OC43, and HKU1) only cause slight symptoms of the common cold. The COVID-19 was quickly discovered to be caused by a coronavirus later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the β coronavirus family. The epidemic of novel coronavirus disease 2019 (COVID-19) was caused by a new coronavirus occurred in December 2019, and now has spread worldwide and turned into a global pandemic.
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