September 11, 2021

Trojan Horses, Pandora's Box, and Gambling with the Variants of COVID19.

Who are the gamblers? Our leaders at many levels, including those managing our workplaces, towns, cities, counties, and states, continue to underestimate the potential outcomes of COVID variant emergence. What many molecular biologists (scientists who work with DNA and RNA) and mathematicians understand is that the very nature of viral replication makes viruses into ever-changing evolution machines. The strain of COVID19 now running rampant through our network of unvaccinated neighbors is far more infective than the ones we dealt with in early 2020. This is the how and why.


Viruses come in many kinds and they all fundamentally work the same way. They are essentially containers that carry a genetic program. Like a box of software on a shelf or on a thumb drive, the virus is just dormant and there, a package that on its lonesome does nothing. Its genetic program, a blueprint encoded in RNA or DNA, is ready to be read and used to guide how to make more of the same virus, but it needs help. That help is a cell, our cells.

If a virus comes into contact with a specific species and type of cell that it can dock onto, it rides freely into the cell like a Trojan Horse and our cells then open up Pandora's box. That RNA or DNA program is set free and our cell's own machinery starts to make proteins that will trigger a mass production line of new virus assembly. Simple and efficient to make and to assemble, just like a Model-T production run. A few thousand copies of the virus can be made and released from a single cell in a matter of hours.

As if massive exponential growth is not bad enough, some viruses like HIV, influenza and COVID19 are just getting started. They have another physical property that will cause them to evolve for maximum efficiency for what they do best: replicating themselves. They will change and evolve. Viruses do this by changing their own program, their own RNA sequence in the case of COVID19, and they do it frequently. 

One of the first virus proteins made by our cells from COVID19's RNA template is an RNA-polymerase, which takes care of making copies of the virus RNA program itself. The problem with this, from our point of view, is that viral RNA-polymerases have low fidelity. They make lots of copy mistakes about every 1/10,000 RNA-bases. Every COVID19 RNA is about 30,000 bases long, so at a rate of 1/10,000 errors, each new virus made in a cell has an average of three changes to its genetic code. So once we are infected, our many cells are making millions and even billions of virus particles that all have slight changes to their RNA sequence. Some of these changes will screw up the function of the virus, many will not seem to have any effect, and some will change the virus' function. Some changes have already changed the COVID19 spike-protein, which docks to our cells, making strains like Delta bind more efficiently and spread illness faster too. At some point, the shape of the spike-protein can also change so that our own antibodies from 2020's Covid19 vaccinations will not block and protect us from future strains. That has already started to happen with the Mu strain which is blocked by current vaccinations but not as well as vaccinations block the earlier strains including Delta.

A reworking of vaccines will be required to tune them to the Mu strain if that strain takes over. Just like we need to have flu vaccines tuned differently each year to match the current strains of influenza viruses. So while community leaders and politicians wish for the best-case scenario as they partially follow the recommendations of public health scientists, the thousands of mutations changing COVID19 RNA every week in just a single person has the potential to keep this pandemic going for a long long time.

The only way to stop it is to prevent the virus from infecting the next person and so on. That is best done with vaccination and masking up, but we are failing to clamp that lid on tight at this point in time and that is why we are now gambling with the variants of COVID19.


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