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Sep. 20, 2021 | Monday
Editorials and Opinions
Dr. Brown: COVID virus keeps outsmarting the human body's defences
Dr. William Brown.

Unlike simple cells such as archaea and bacteria, viruses such as SARS-CoV-2 (which causes COVID) are unable to make copies of themselves without host cells to exploit.

Like most viruses, SARS-CoV-2 is a bare-bones lifeform, comprised of the minimum genetic material (RNA for corona viruses) necessary to code for the small number of proteins typical of most viruses (about 20 for SARS-CoV-2), a glycan sugar coating for SARS-CoV-2, and of course, its own RNA.

That’s it, nothing like the complicated machinery of the simple of cells like bacteria. 

But as simple as viruses appear to be, they are capable of identifying specific target sites embedded in the membranes of host cells, penetrating them and taking over the metabolic machinery of the cell to churn out copies of the virus by the thousands.

In the case of SARS-CoV-2, understanding the precise sequence of these events has been a challenge for scientists looking for weaknesses in this virus that could be exploited in the development of future vaccines to keep up with new variants.

We understand the initial steps best. The scattered 10 to 20 spikes that stud the surface of the SARS-CoV-2 virus are made of several highly specific proteins coated with a sugary compound (glycan) to shield the underlying highly antigenic proteins from the immune system. Score one for the virus.

Modern technology has made it possible to create high-definition 3-D models of the spikes, identify the precise location of new mutations and figure out whether those mutations, because of their locations, might offer advantages to the virus by increasing the ease with which it can contact and penetrate host cells and hide from the immune system.

SARS-CoV-2 spikes twist and turn in their search for their targets – ACE-2 receptors – which are found most commonly embedded in the membranes of cells that line the respiratory tract, heart, blood vessels and the gastrointestinal tract – the distribution of which, explains the symptoms and pathology of COVID-19.

Once close to an ACE-2 receptor, the tip of the spike extends to lock onto the receptor and fuse with the cell membrane, after which an enzyme released by the host cell punches a hole in its own membrane to open the door for the virus to enter the cell. Score 2 for the virus.

When SARS-CoV-2 is inside the host cell, events become much more complex and risky for the cell. We know the virus is capable of turning off the cell’s own alarm system and response to the threat. That’s bad enough.

But the virus also stops the production of proteins for the cell’s own purposes by blocking the transfer of the cell’s protein-encoding mRNA from the nucleus into the cytoplasm. As well, whatever nuclear mRNA makes it into the cytoplasm is blocked from entering the ribosomes for translation into the cell’s proteins by a molecular code-sensitive password at the entrance that allows only mRNA of viral origin into the ribosomes where proteins are made.

In these and other ways, SARS-CoV-2 subverts the cell’s metabolism and redirects it to making thousands of copies of the virus’s proteins, glycan and, of course, its own RNA. Score 3, 4 and 5 for the virus.

The assembly of the viral parts into complete viruses takes place in pathologically dilated spaces within the endoplasmic reticulum in the cell’s cytoplasm. The freshly minted viruses are packaged within the cell’s Golgi apparatus and lysosomes (the cell’s garbage system), which deliver the viruses to the membrane of the cell, where thousands per cell escape through gaps in the cell membrane, into the circulation.

On the way out of the host cell, the spike proteins of the new viruses are activated and ready to go about the business of repeating the cycle again and again, each time destroying more and more host cells. Score 6 and 7 for the virus.

Believe it or not, that’s a very brief summary of the life cycle of the SARS-CoV-2 encounter with host cells. However, bewildering this account may be, it only hints at the complexity of what this supposedly simple virus, with a genome only 30,000 base pairs long, is able to do.

Much remains to be sorted out. It’s important work if we’re ever going to identify and exploit the virus’s genetic and molecular weak points to develop effective antiviral agents and update current vaccines.

For surely there will be other variants well beyond Delta, some of which may require major rejigging of our vaccines and vaccine programs throughout the world. The virus wins 7-0.

Dr. William Brown is a professor of neurology at McMaster University and co-founder of the Infohealth series at the Niagara-on-the-Lake Public Library.