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The SARS-CoV-2 virus

This article will present the SARS-CoV-2 virus, causative agent of COVID-19 and the current pandemic.

SARS-CoV-2 is an RNA virus. RNA can be either single or double stranded and the SARS-CoV-2 genome is composed of single stranded RNA of just under 30,000 bases.

Next week in steps 2.5 and 2.6, we will focus on the spike protein and how this enables the virus to enter the host cell. Here we will look at what happens next. To enter into a cell, the virus must recognise and bind to a receptor. SARS-CoV-2 Spike uses as receptors two specific cell-surface proteins (ACE2 and TMPRSS2), most frequently found on cells in the upper and lower respiratory system. After entering host cells, the SARS-CoV-2 genome uses the cell machinery to produce copies of itself. In this process, called replication, the virus multiplies its RNA genetic code and generates its proteins. Two large proteins (ORF1a and ORF1b) are generated and will be broken down into the non-structural viral proteins (nps1-16). The genome also encodes the structural proteins Spike (S), Envelope (E), Membrane (M) and Nucleoprotein (N) and a few other proteins that interact with the cell function (Figure 1).

SARS-CoV-2 genome and proteins. A sferic viral particle in the centre of the image. A surrounding arc indicates the viral genome organisation: Open reading frame (ORF) and genes of the non-structural proteins 1 to 16 in shades of blue. In shades of green: structural genes Spike, Envelope, Membrane, and Nucleocapsid. Surrounding the arc there are illustrations of 3-dimensional structures of non-structural and structural viral proteins corresponding to the genes Figure 1. An Schematic illustrating the SARS-CoV-2 viral particle in the centre. The surrounding arc depicts the genome organisation. Structural and non-structural viral proteins are coloured in green and blue shades, respectively. Source: RCSB PDB

All these pieces are then assembled into new viral particles and released from the cell to infect new cells. Some viruses may enter the bloodstream and find their way to organs other than the lungs such as the heart, brain and kidney. This may cause additional damage and wide-ranging symptoms.

Figure 2 shows a schematic of SARS-CoV-2 replication within the host cell as well as the route from lungs to secondary organs. Also shown are components of the host immune system which act to destroy the virus. Learn more about the different components of the immune system.

Diagram showing the replication cycle of SARs-CoV-2. The viral particle binds with the ACE2 receptor and allows the viral genome to enter the cell. TMPRSS2 proteases translate the RNA into proteins forming the structure of new viral particles as well as ssRNA which facilitate replication of the viral genome. Fully assembled viral particles are released from the cell and may infect nearby cells or enter the bloodstream and head to secondary organs such as the brain, heart, liver, spleen, colon and kidneys

Figure 2. The SARS-CoV-2 replication and pathogenesis. (a) The SARS-CoV-2 infects the upper and lower respiratory tract. (b) The virus replication from 1 to 12 has been described as: (1-2) The virus identifies the ACE-2 receptor. (2) The Spike (S) protein of SARS-CoV-2 binds to the ACE-2 receptor. (3, 4) The virus-receptor internalization occurs and a membrane fusion is carried out followed by the release of the viral genome inside the cell. (5–7) Replication of viral genetic code and generation of viral proteins. (8–10) Assembly of new viral particles. (11–12) Budding of recently formed viral particles from the infected cell. (c) The virus disseminates to the other part of the body through blood affecting the brain, heart, liver spleen, large intestine and kidneys. Source: Respiratory Research

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The Power of Genomics to Understand the COVID-19 Pandemic

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