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Coronaviruses (CoVs) – SARS-CoV & SARS-CoV-2 [2019-nCoV]

Coronaviruses (CoVs) are enveloped non-segmented positive-sense RNA viruses infecting human and vertebrates. They are classified into four types (genus), α-CoV, β-CoV, γ-CoV and δ-CoV. They can infect the respiratory, gastrointestinal, hepatic and central nervous system of human and many wild animals. The family of Coronaviridae constantly circulates within the human population and mainly causes mild respiratory diseases. Recently, a new severe acute respiratory syndrome β-coronavirus called SARS-CoV-2 (or 2019-nCoV) has emerged, which causes an epidemic of acute respiratory syndrome called coronavirus human disease 2019 or COVID-19. Typical clinical symptoms of these patients are dry cough, fever, breathing difficulties, headache and pneumonia. Disease onset may result in progressive respiratory failure, heart tissue damage and even death.

SARS-CoV-2 Structure

SARS-CoV-2 shares 79.5% sequence identity with SARS-CoV and is 96.2% identical at the genome level to the bat coronavirus BatCoV RaTG133, suggesting it had originated in bats. The coronaviral genome encodes four major structural proteins: the Spike (S) protein, Nucleocapsid (N) protein, Membrane/Matrix (M) protein and the Envelope (E) protein (see Figure 1). The SARS Envelope (E) protein plays a role in viral budding and virion envelope morphogenesis. The SARS Membrane/Matrix (M) protein is one of the major structural viral proteins. It is an integral membrane protein involved in the budding of the viral particles and interacts with SARS Spike (S) protein and the Nucleocapsid (N) protein. The N protein contains two domains, both of them bind the virus RNA genome via different mechanisms.

The CoV Spike (S) protein assembles as trimer and plays the most important role in viral attachment, fusion and entry. It is composed of a short intracellular tail, a transmembrane anchor, and a large ectodomain that consists of a receptor binding S1 subunit and a membrane-fusing S2 subunit (see Figure 2, adapted from Cell, Hofmann, et al. (2020)). The S1 subunit contains a receptor binding domain (RBD), which binds to the cell surface receptor angiotensin-converting enzyme 2 (ACE2) present at the surface of epithelial cells.

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