Often during virus outbreaks, conspiracy theories arise which purportedly explain the emergence of the virus. These range from deliberate government release as an agent of population control to Illuminati concocted plagues designed to disrupt our way of life in order to usher in the New World Order. The Covid-19 pandemic is no exception and there has been a wave of conspiracy theories relating to SARS-COV-19, the virus behind Covid-19. Writing in NatureKristian G. AndersenAndrew Rambaut , Ian Lipkin, Edward C. Holmes  and Robert F. Garry sought to investigate the origins of SARS-COV-2, not only in order to dispel some of these theories, but also because during a pandemic it’s important to know where the virus came from as this may inform future preventative strategies. 

Read the article yourself here: https://www.nature.com/articles/s41591-020-0820-9

The authors first start by analysing the receptor binding domain (RBD) of the SARS-COV-2 spike protein. This protein is present on the outside of the SARS-COV-2 virus particle and is responsible for the binding of the virus to the receptor ACE2, which is found on the surface of cells. It’s this protein which the virus exploits to enter our cells, and it’s been shown to be very important for coronavirus host range and pathogenicity. 

Spike proteins are present on the outside of the virus particle which bind with to ACE2 receptors on the outside of our cells.

While it’s clear the SARS-COV-2 RBD is able to successfully bind the ACE2 receptor found in human, ferret and other similar species, this interaction is not exactly perfect. In fact, SARS-COV-2 binds with less efficiency than SARS. If a super plague was generated in a lab, computational studies could have been carried out to formulate better binding of ACE2, therefore improving the infectivity of the pathogen. Pretty sloppy work, Illuminati. It’s much more likely that the RBD of SARS-COV-2 evolved to bind a human-like ACE2 and has been acted upon by natural selection. What do I mean by a human-like ACE2? Remember that we share about 98.5% of our DNA with chimps and around 85% with mice, so its highly likely that SARS-COV-2 evolved to infect a similar, but different species, which provided it with some limited ability to infect humans. Once this human transmission was set up natural selection can allow the virus to adjust to humans in order to infect us more efficiently – more on that later. 

There’s also good evidence that SARS-COV-2 wasn’t generated in a lab due to the fact it doesn’t appear to have been designed according to other viral “reverse genetics” systems. Reverse genetics systems are what scientists use to produce genetically manipulated viruses in the lab. These techniques employ the use of the virus genetic material which has been probed and packaged through a variety of molecular techniques which allows infectious virus to be generated. The authors make it quite clear that SARS-COV-2 shows no evidence of being generated by the use of these existing virus reverse genetics systems. So, if SARS-COV-2 is naturally occurring, how did it infect humans in the first place and start the whole pandemic off? 

The authors provide two hypotheses:

1) The virus arose in animals and, through natural selection, acquired the necessary genetic changes needed to infect humans, whereupon it jumped the species barrier and infected people. 
 
Or 

 2) The virus jumped from an animal species into humans, whereupon it spread through the human population and, through natural selection, acquired the genetic changes needed to successfully cause a pandemic. 

By comparing the genetic material of SARS-COV-2 and other coronaviruses which have been sampled from different species, it has been shown that SARS-COV-2 shares high sequence similarity with those coronaviruses found in bats. The Huanan market in Wuhan is considered to be ground zero for this pandemic and it is known that bats were stored and sold here, in addition to a myriad of other species. It is therefore highly probable that one of these species was host to the progenitor of SARS-COV-2, which then found its way into the human population. 

Interestingly, the RBD of SARS-COV-2 is unlike those found in bats but shares high homology with those found in pangolins. Pangolins are an endangered, and very cute, little species of mammal which are the most illegally trafficked animals in the world. Coronaviruses isolated from these creatures exhibit RBDs with high similarity to those found in SARS-COV-2. Pangolins are also thought to have been present at the Huanan market in Wuhan. 

A very cute, pangolin. https://ichef.bbci.co.uk/images/ic/640×360/p066n3f4.jpg

Coronaviruses are also known to undergo genetic recombination, in which they swap genetic material. This happens when two different coronaviruses find themselves infecting the same host. It’s therefore highly likely that SARS-COV-2 arose from a recombination event between two coronaviruses, possibly from bats and pangolins, which was then able to jump into humans. 

There’s one more feature of SARS-COV-2 that the authors draw attention to: the addition of a polybasic cleavage site which sits between the two subunits of the spike protein. This site is unique to SARS-COV-2 and may result in efficient cleavage by cellular proteases such as furin. This sounds quite complicated. Simply, the virus has evolved a site in the portion of the virus which is responsible for invading our cells which improves its ability to function, therefore making it more infectious. 

We see such adaptations in avian influenza all the time – they arise through natural selection when flu spreads through chicken populations. Such adaptations result in the generation of highly pathogenic bird flu strains and are a major public health concern. Mutations of this type which affect the spike protein subunit junction have also been found in nature many times before. These inserted residues also change the structure of the spike protein slightly in a way that the authors hypothesise may help the virus evade the host immune response. 

“OK, so where did this genetic change come from? Is it possible for this to happen in the lab? Can it happen in nature?” 

Simply, both are possible, but one is less likely. Looking at our two theories it’s entirely possible that this mutation, which likely allows for increased pathogenicity, arose during repeated human to human transmission, similar to what we see in birds with flu. This would mean that, after making the jump from bats/pangolins/unknown species to human, SARS-COV-2 spread through the human populace, acquiring this mutation, and then setting off the chain of events which led to the pandemic. We see this in SARS often, in which the virus jumps from camels to humans and then spreads from human to human for a short period. Crucially SARS has not yet been able to sustain its human-human transmission, whereas SARS-COV-2 has. It’s also possible that this mutation arose in the progenitor to SARS-COV-2 in an animal host. To have arisen this would require sustained transmission between hosts that are in high density and have human-like ACE2 receptors. 

Both theories are plausible…

What isn’t as likely is that the virus gained this adaptation in a laboratory setting. In labs around the world viruses are routinely grown in cell culture. Viruses are introduced to cells in culture, allowed to grow, and eventually harvested. This is known as “passage”. For this mutation to arise in cell culture the virus must have been serially passaged through cells which contain a human-like ACE2 receptor. While these passages take place, the virus is continually evolving, so much so that serial passage in cells eventually leads to viruses getting so good at infecting cells in culture they become worse at infecting whole animals. It’s theoretically possible that the virus could have been serially passaged through an animal, one which contains sufficiently human-like ACE2, however this has never been documented. 

It is very unlikely that SARS-COV-2 originated in a laboratory setting

…and it doesn’t exhibit the genetic fingerprints we’d expect a genetically modified super plague to exhibit. Unfortunately, at the moment all we can do is theorise about its origins until the exact host, or progenitor virus, is found. There are a staggering number of viruses present in nature which we simply haven’t discovered yet (think of a tip of the iceberg kind of thing) which are currently quietly circulating in animals, and possibly humans, throughout the world. The conditions which we saw at the Huanan market in Wuhan in which various different exotic animals are stacked, live and dead, in cages in close proximity to each other, and humans, makes the perfect melting pot for these pandemics to arise. Furthermore, as humans clear more habitat, and as global temperature rise allowing vector species such as mosquitos and midges to extend into higher latitudes, it’s a matter of time until this happens again. While this pandemic is ongoing, the next one in line is lurking out there and it’s vitally important that we learn what we can from SARS-COV-2 so that we are prepared when it finally emerges. 

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Coronavirus: A natural phenomenon or a man-made weapon? Read a lay summary of @NatureMedicine article: The proximal origin of SARS-CoV-2 by @K_G_Andersen, @arambaut and @edwardcholmes and co. Written by @jordandoesflu with @thescisocial #covid19 #sarscov2 #mythbusters https://thesciencesocial694680041.wordpress.com/?p=104

Written by Dr Jordan Clark