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SARS-CoV-2 virion has an enveloped spherical structure, with a diameter of approximately 120 nm. SARS-CoV-2 virus genome is encapsulated in a helical capsid formed by a nucleocapsid (N) protein. The viral genome and helical nucleocapsid are encapsulated by a lipid bilayer comprising spike (S), envelope (E), and membrane (M) proteins.
The SARS-CoV-2 viral genome is a single-stranded positive-sense RNA (ssRNA(+)) with approximately 29,903 nucleotides in length. The virion consists of a total of 12 open reading frames (ORFs), including 4 structural protein ORFs (S, E, M, and N), and 8 nonstructural protein ORFs (ORF1a, 1ab, 3a, 6, 7a, 7b, 8, and 10). The S protein of SARS-CoV-2 binds to a human receptor called ACE2 (angiotensin-converting enzyme 2), enabling intracellular infection and the formation of neutralizing antibodies, and is also relevant to viral genome evolution.
S protein of SARS-CoV-2 virus consists of S1 and S2. S1 interacts with and binds to the host cell receptor, ACE2. The SARS-CoV-2 virus then fuses with the host cell membrane, undergoing a process that includes the proteolysis of S1 and S2 mediated by acid-dependent proteases such as furin, cathepsin, and trans-membrane protease, serine 2 (TMPRSS2). As the viral genome is released into the cytoplasm, the viral polymerase translates the replicase enzyme, thereby initiating the replication, and two polyproteins, pp1a and pp1ab, are translated. Nonstructural proteins are then produced leading to the assembly of replication-transcription complexes (RTCs). RNA replication and sub-genomic RNA transcription have progressed over time. The viral membrane-binding structural proteins (S, E, and M) are translated and transported to the middle compartment of the ER-Golgi complex. After viral assembly, the virions are transported by the basic cell secretory pathway and released to the outside of the cell.
