Lots of coverage is given to talking about how ‘the coronavirus’ could mutate and spawn new and ever more deadly strains – this despite it apparently already being the most deadly virus in the history of the world ever, which you would think doesn’t really leave it any scope to get worse – as part of the relentless but increasingly desperate government strategy of wanting to keep you all afraid. Any virus evolves on a near constant basis and viral evolution through its natural selection is an essential part of its desire to survive.
Evolution by natural selection can be random or more programmed. Random errors can occur in the translation of a virus’ RNA resulting in inaccurate replication of its genetic sequence. You can observe how this works by opening an online language translator and translating a paragraph from English into a different language: then paste the translation into the original box, reverse the languages and translate the translation back to English. Repeat this just a few times and you quickly start to see differences appear. In effect you are seeing mistranslation, something known as tRNA wobble in virus terms.
Programmed changes can occur where a virus alters its physical structure or appearance, for example to make itself more effective at its own reproduction (colonisation) or to make it harder for the body’s immune system to detect & destroy it (immunoevasion). The virus doesn’t wake up in the morning and decide to hide from one particular host’s immune system but rather the changes are programmed into its genetic sequence.
In addition to evolution through its natural selection, a virus can evolve through reassortment and recombination. Reassortment is when two viruses from the same parent virus find themselves in the same host and swap genes from their respective genomes. Recombination is when two viruses from different parents come together in the same host and through their replication produce something new with bits of one virus finding themselves mixed together with bits of the other. One of the two viruses may be from the host itself, particularly where the host is a natural virus reservoir for that virus.
Some viruses are particularly prone to reassortment, notably within the orthomyxoviridae family, where avian, swine and human strains of the influenza A species of virus often reassort. Reassortment played a key part in recent global influenza pandemics, such as those in 1918, 1957, 1968 and 2009 (the latter being involving multiple reassortments between human and swine subtypes of the virus).
Many animals are natural reservoirs for viruses, with the host species carrying the virus without it being pathogenic to them. It is commonly-known that bats are natural virus reservoirs for several coronaviruses with SARS-CoV-2 having a most recent common ancestor in bat coronavirus RaTG-13, with which it shares 96% genetic similarity [Patiño-Galindo et al]. However given the differences between humans and chimpanzees who share a 98% genetic similarity, 96% isn’t close enough for a cigar.
The key to understanding SARS-CoV-2’s pathogenic nature is its distinctive spike or S glycoprotein. This is what allows the virion firstly to bind to cells (through the S1 unit of the S protein’s receptor binding domain (RBD)) and secondly to gain access to the cell (through the S2 unit of the RBD), whereby it achieves intracellular fusion and it goes about making lots of new copies of itself. The S protein and its related RBD are the components of SARS-CoV-2 that are most likely to be subject to recombination as these relate most effectively to its ability to survive by binding to host cells and then fusing with them. One without the other is useless: an existing coronavirus could bind to a particular type of human cell but without the ability to gain cellular entry it would just sit there. Likewise, a coronavirus with the capacity to enter a particular human cell but without the ability to receptor bind would bounce around without being able to attach.
One coronavirus – betacoronavirus MP789 – is carried by pangolins as natural reservoirs. MP789’s spike protein genetic sequence is at least 98% similar to that portion of SARS-CoV-2’s and much was made initially about SARS-CoV-2 having jumped from bars to human via pangolins (one spillover event and one intermediate host) or from bats to pangolins to humans (two spillover events). Knitting all this together, you can suggest an outline of the evolution of SARS-CoV-2, again with acknowledgement to the work Patiño-Galindo et al, along these lines:
- An existing betacoronavirus recombines with another coronavirus and gains the RBD, possibly from an evolved variant of SARS-CoV. This happened prior to 2009 and was likely in bats.
- After 2009, a second recombination occurs between the bat coronavirus and pangolin coronavirus MP789. This recombination evolves the RBD further, providing the S1 or S2 unit. If only one of these components of the S glycoprotein is present then the virus is not pathogenic to humans. It both are present through the second recombination then it may be pathogenic but as with SARS-CoV-1, its spread is likely to be limited because it is not that transmissible.
- After 2013, there is another recombination with a different virus that contains a furin cleavage site. This enables the ‘activation’ of the virion through the presence of the enzyme furin, which is present in the human airway. A furin cleavage site didn’t exist in the evolving virion at this point and wasn’t in SARS-CoV but one does exist in two other betacoronaviruses that are pathogenic to humans; CoV-OC43 and CoV-HKU1. It is also present in influenza A so it is logical that it had to be introduced through an additional, third recombination.
- Therefore at some point after 2013, the virion possesses its RBD, S1 and S2 units and a furin cleavage site with the addition of the latter likely to be the point at which it becomes capable of being pathogenic. While it may have been named SARS-CoV-2 and given the ‘novel’ status in early 2020, it had already been around for a period of years in which case it is more accurate to describe it as ‘newly-discovered’ and it is equally likely that it was circulating for a few years and infecting people before it came to the world’s attention in late 2019. This is key as it means you need to ‘start the clock’ on SARS-CoV-2 long before it was first classified and described as a novel coronavirus in early 2020: it has been around for much longer, with many, many more individuals having had the virus than simply those from when you start the clock earlier this year.
- Remember that annoying mild-flu like cough a couple of years ago that was more than a cold but less than flu? Given the presence of a furin cleavage site in influenza A virus subtypes, that may have been the point at which the final piece in SARS-CoV-2’s evolution fell into place. Up until that point it was a ‘heavyweight’ virus that was more dangerous (like SARS-CoV-1) but which lacked the means of transmission and would have been localised, like both SARS-CoV-1 and MERS.
- After that point, it recombined with a ‘lightweight’ virus that was very transmissible as a result of its furin cleavage site – like seasonal/winter flu or even the common cold – but which as a consequence was no more dangerous than them.
This series of recombinations culminated in a SARS-like virion piggybacking or hijacking another existing virion, in order to gain greater mobility and enhanced transmission. But these factors come at the expense of strength.
In effect you have two different functions to the virus: Function A is what most people get and as we identified recently here, 99% of people are in this category. They are asymptomatic or experience mild to moderate symptoms and the infection is dealt with effectively by the innate immune system. The adaptive immune system is not required and so no antibody production occurs, which is why a significant proportion of people who have had the virus test negative for antibodies, as we have covered here.
For those with comorbidities, compromised immune systems or high viral load – the remaining 1% – Function B affects the respiratory system as the RBD binds to the ACE2 present on the membrane of epithelial cells in the lungs, potentially leading to viral or bacterial pneumonia.
It is important to highlight that this combined function of SARS-CoV-2 is still less dangerous than seasonal or winter flu with a mortality rate of 0.06% compared to 0.1% (source: Johns Hopkins Coronavirus Resource Center /Worldmeters/WHO) and that overall, SARS-CoV-2 is a low pathogenic disease. Remember that one of the only correct actions by Public Health England (soon to be renamed as the National Institute for Health Protection, in a clumsy attempt to make people forget its name and central role in the genocide of tens of thousands of people) was on 19th March when it downgraded SARS-CoV-2 from high to low consequence infectious disease.
In understanding how SARS-CoV-2 came into being and what it is, you understand what it is not. It is not what the government told you it was, it was never anything of the sort.