Capsule 5 : How does the coronavirus replicate itself?

27 April 2020 Julian Venables

Capsule 5

How does the coronavirus replicate itself?

by Julian Venables and Philippe Fort

As we have seen, the virus’s genetic material is made of RNA, a molecule that is very similar to the DNA in our cells. The viral RNA contains about 30,000 letters, about 100,000 times less than the DNA of the cell it infects, which has 4 billion letters! Nevertheless this little addition of genetic material is enough to cause considerable damage. Once in the cell, the viral RNA has two jobs: to make copies of itself and to oversee production of viral shells, in which to package the copied RNA. These two tasks will thus make mature viral particles to be liberated from the cell. What happens then when the viral RNA penetrates in the cell? The first priority of the virus is not to make the Spike protein. That protein will be on the surface of the new viruses and can be made later. No, the priority is to multiply its RNA to start taking over the cell. The stages of infection are thus the following.

First the ribosome of the cell produces the proteins coded by the two biggest genes on the viral RNA. These two proteins get together to form the ‘replicase’ complex, which can copy (replicate) the RNA into an ‘anti-sense’ strand. This will then be re-copied lots of times into sense-strand viral RNAs. The replicase complex allows massive production of viral RNA in the ‘flesh’ of the cell (the cytoplasm) without having to make the perilous journey into the heart of the cell (the nucleus), where the tools to copy the cellular DNA reside.

When enough viral RNA has been copied in the cytoplasm, the eight other genes can be translated. These include regulatory genes whose sole role is to inhibit the translation of cellular genes. The ‘structural’ genes destined to make new viruses can also be translated at this point, including the Spike protein (S) that makes the corona, which will help the virus infect new cells, the Envelope protein (E) that helps the virus escape the cell, the membrane protein (M) that maintains virus structure, and the nucleocapsid (N) protein that provides the glue between the viral RNA and the M protein, to hold the RNA in the particle.

Once built, the 4 structural proteins hitch a lift on the normal cellular secretory pathway. While in transit, they roll themselves with viral RNA and cellular lipids. At the cellular exit point they have become mature viruses, ready to leave the cell and attack and colonize other cells and people.

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