This essay was prompted by a friend who asked some really important questions about how COVID-19 is mutating and trying to evade our immune response.
Viruses have no “brain”, they have no volition to “evade”. Viruses are very simple organisms with a very small set of proteins, most of which are only expressed inside the cell and are never even seen by the immune system.
What are proteins and how are they different from RNA?
Both proteins and RNA are like strings of beads. Each string has a very specific arrangement of those beads. But the beads on the RNA strings are completely different than the beads on the protein strings. You can imagine that the RNA might be strings of pearls of 4 different colors, while proteins are more like strings of flowers with 20 different flowers linked one to the other at the stems.
RNA and DNA are very similar, each being a string of 4 different color beads, but in RNA one of the colors is different than one in DNA (think of RNA having Blue, Green, Yellow and White, while DNA has Blue, Green, Yellow and Red). Also, as you might remember, DNA is a “double helix”, like two snakes wound around each other, while RNA is only one string. DNA stays in the nucleus of the cell (a distinct and isolated “room” in the cell, while RNA leaves that room and circulates in the general area inside the rest of the cell.
mRNA, or “messenger” RNA is manufactured in the control room (nucleus) working off of a very specific template on the DNA molecule and then exported outside the nucleus to the cell and acts as the “message” sent from the boss in the control room to the cell on what protein to fabricate by the factory in the cell.
The mRNA message for how to build viral proteins mutates on a very regular basis; for COVID this is 1 “base mutation” per 100,000 replications. A good way to understand this is that when the mRNA is reproduced inside an infected cell, the “typist” making the new copy makes a typo once every 100,000 times that they write the same sentence (an mRNA molecule).
From the standpoint of the cell and its mechanisms that assemble proteins you can visualize an assembly line. There are buckets of each of the 20 amino acids (different flowers) waiting to be assembled into a protein. The assembly line workers get an “order” from a piece of mRNA. They look at that mRNA and the first thing they search for is a symbol that says, “START HERE”, just like you see a capital “T” at the start of this sentence. You know the sentence starts there because there is a capital letter. You know that it will end when you see a period. Likewise, the assembly line knows when the protein is finished when it sees a symbol that says, “STOP NOW”.
Once the line workers see a “START” symbol, they then start reading the directions for which amino acid with which to start the chain. The instructions on the RNA strand consist of 3 beads each. So, after the start signal, they might see a Green, Green, Blue grouping (called a codon). That codon says:
“put a red rose here”. The workers now know that they need to start with that specific amino acid (flower). Different codons code for different amino acids. For the 4 different color beads, there are a total of 63 different possible combinations. One of these combinations means “START”, 3 of them mean “STOP”. With a choice of 20 amino acids that leaves 59 different codons, and that means there are several different codons for each of the 20 amino acids.
The cell mechanisms thus create a protein of amino acid beads from the template on the RNA of base beads.
As I mentioned above, the mutation rate for COVID-19 is about 1 base per 100,000 replications. As you can see, changing a “Green” bead to a “Blue” bead will change the codon and therefore change the instruction to the cell of which amino acid to insert at that specific location.
The most important thing to remember is that this is totally random. There is no external factor that influences what mutation will occur.
Some “typos” merely change the codon from one that links to a specific amino acid to one that links to the same amino acid. These mutations are “neutral”; they have no effect on the arrangement of flowers on the protein.
Some “typos” create proteins that are NOT functional. Think about a codon that has been changed to mean “START” or “STOP”. Those mutations will prevent the protein from being constructed at all, and those mutated viruses simply die out and won’t replicate.
Some mutations change the message of which amino acid “flower” to place in a specific location in the protein chain. Some of these have no effect on either the function of the protein or the ability of our immune system to recognize that protein.
But sometimes the mutation will change the ability of the protein to perform its function. For those proteins inside the cell, these mutations may make the virus less able to replicate, and those mutations would result in the death of that virus variant. But some of those mutations may allow the virus to be able to replicate better, raising the amount of virus shed into the blood and perhaps increasing the viral load that is expelled by the individual. This could lead to an increased “infectivity” of that variant giving it some advantage in the population because there would be more of that virus than preexisting variants. It will outrace the pre-existing strain and take over.
For the proteins on the virus surface, those that are the targets of vaccines and your own immune responses, sometimes, and I really mean sometimes, that single amino acid change in the protein will result in a change in the ability of the existing immune response to recognize and neutralize that new strain.
Maybe a little explanation of how proteins do what they do would help here.
As I said above, a protein is a string of amino acids like a string of beads. Each amino acid has unique properties. Some are large, some small; some have a positive charge, some a negative charge; some like to bind to water molecules (polar, like vinegar), some push water molecules away (non-polar, like oil). The string of amino acids, therefore, have a lot of competing parameters and the sum of all of those parameters results in the protein arranging itself into a very specific shape. This is called the protein conformation.
It is the conformation of the protein that results in its activity. For enzymes, the protein attains a shape that allows some specific molecules to bind to it and then react to transform those other proteins. For example, the enzyme lactase binds to the sugar lactose and breaks it into its two sugars, galactose and glucose. If you don’t have that enzyme, you can’t break down the lactose and you have digestive problems (lactose intolerance).
For a hormone, it is the conformation that allows it to be recognized by a binding site on a cell.
For the immune system, it is the conformation that is recognized by the antibody (whose conformation at the tips of its arms is its binding site and needs to be the mirror image of the antigen).
For the Spike protein on the COVID-19 virus, the binding domain on that protein is the one that allows the virus to attach to the target cell. If the change in the conformation results in a “better” binding site (i.e., a higher binding energy), then that virus will out-compete the other strains. If the change results in a “worse” binding site, it will disappear. For those new Spike proteins that are “better”, the conformation may or may not affect the ability of the antibodies to still recognize the protein. Some of the antibodies bind directly to the binding site on the Spike protein, some bind to other parts of the Spike protein. The existing immune response may be restricted, but the new conformation will also stimulate new antibody responses.
You can see that single mutations result in limited changes. That is why you may hear about some of the new variants having multiple mutations. It is the accumulation of these new mutations that can result in the ability to reinfect vaccinated individuals. Still, the existing immune response in the large majority of cases will prevent severe symptoms and hospitalization.
And these emerging strains with multiple mutations may arise from an infection in a patient with a repressed immune response such as those with AIDS or under immune suppression therapies due health issues. In those individuals the COVID-19 virus can continue to remain active for months, accumulating multiple mutations before released into the environment
It is also always to remember that NONE of the vaccines are 100% effective. Even at wonderful levels of response, almost unheard of, there is still a small fraction of people who, although vaccinated, are still susceptible to infection.