SARS COV-2 # Corona virus# Covid 19# structure# transmission# symptoms# life cycle# Genes & Genus

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SARS COV-2 # corona virus # covid 19 # novel corona virus# structure of corona virus # mode of transmission # infection # symptoms # life cycle of corona virus # Diagnosis # Treatment # Genes & Genus

A coronavirus virion (a virus particle that infects a host) goes through a replication life cycle within a host cell, thereby creating more copies of itself that can eventually infect more cells. SARS-CoV is the causative agent responsible for the 2003 SARS epidemic and an example of such a coronavirus infecting a human cell. The virion responsible for the new coronavirus outbreak in 2019 (COVID-19) is called SARS-CoV-2 and is closely related to SARS-CoV. Its life cycle, and how the disease develops, have yet to be fully resolved.

The key stages of a general coronavirus replication life cycle include binding to a host cell surface receptor, cell entry, virion uncoating, translation of replicase proteins, RNA transcription, RNA synthesis, virion assembly, and release of mature virions into the extracellular space, where the cycle can begin again.

The virion is an enveloped particle surrounded by a protein shell. This shell, called a capsid, is made up of spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, containing the single-stranded RNA genome. This RNA molecule is 28 to 32 kilobases (kb) in length and a "plus-strand RNA" with positive polarity, which means that it can be translated directly into protein. The S, E, M, and N proteins are all structural proteins. The spike proteins on the capsid give corona viruses their distinctive “crown” or “solar corona” appearance under electron microscopy. They are crucial in determining cell tropism (which type of host tissue can be infected) and host species specificity (which host species can be infected). For virion replication to begin, the spike proteins first bind to specific host cell surface receptors that are embedded in the host cell membrane - a process called host cell recognition (Step 1). In the case of SARS-CoV, this receptor is angiotensin-converting enzyme 2 (ACE2). ACE2 is a regular cellular protein that happens to be used by the virus to gain entry to the cell. It has been been confirmed that the new coronavirus SARS-CoV-2 also binds to ACE-2 and structurally resembles SARS-CoV.

Once the binding between the spike protein and the receptor is complete, the virion enters the cell through one of two processes. Step 2a: membrane fusion from without where viral and cellular membranes fuse and the RNA genome of the virus gets access to the cytosol. Step 2b: endocytosis where the receptor-bound virus is enveloped by the cell membrane and enters the cytosol within a vesicle. Following either route of cell entry, the viral RNA genome is released into the cytoplasm (Step 3), which is followed by uncoating of the RNA (Step 4).

Once in the host cytoplasm, a replicase gene on the RNA strand is translated into two replicase polyproteins (Step 5). Translation is the production of proteins from RNA, and a polyprotein is a large protein that can be cleaved into smaller proteins. The polyproteins are further processed by viral proteinases (enzymes that break down proteins) to yield individual replicase proteins (Step 6).

These replicases mediate the production of full-length negative-strand RNA, which later serves as a template for positive-strand virion genomic RNA (Step 7). In contrast to plus-strand RNA, negative-strand RNA is complementary to the mRNA and cannot be translated directly. It needs to be converted to plus-strand RNA by RNA polymerase first. The full-length negative-strand RNA is transcribed to produce shorter mRNAs (Step 8). These shorter mRNAs code for the structural proteins (e.g., S, E, M, and N) and nonstructural accessory proteins, including the viral proteinases, during translation (Step 9).

The newly produced plus-strand viral genomic RNA as well as nonstructural and structural proteins are translocated (Step 10) to assembly sites at a transitional zone between the endoplasmic reticulum (ER) and the Golgi apparatus. The Golgi apparatus and the ER are both organelles involved in protein synthesis, post-translational modification of proteins, protein packaging into membrane-bound vesicles, and protein transport. Here the new virions assemble (Step 11), start maturing, and bud off from the Golgi membranes as vesicles (Step 12). These vesicles are translocated to the host cell membrane (Step 13) where they fuse with the host cell membrane and are released into extracellular space (Step 14). This release process does not rupture the host cell and is called nonlytic exocytosis.

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