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How the Genome Proves That SARS-Cov-2 Arose Naturally

by Abigail Brooke

The claims that the novel coronavirus causing the current pandemic was engineered in a lab and perhaps even deliberately released have been all over the internet. However, a new study using genomic analyses debunks these claims, providing scientific evidence that the novel coronavirus arose naturally, with the researchers stating that ‘our analyses clearly show that SARS-Cov-2 is not a laboratory construct or a purposefully manipulated virus’.

The findings, published in the journal Nature Medicine, are the result of an international research team, partly supported by the NIH. Kristian Andersen, Scripps Research Institute, La Jolla, CA; Robert Garry, Tulane University School of Medicine, New Orleans; and their colleagues worked together to compare publicly available genomic data from several coronaviruses, including the new one that is the cause of Covid-19. Here, sophisticated bioinformatics tools were used to analyse the genomes of the different coronaviruses.[1]

Mutations in the Receptor-Binding Domain of SARS-CoV-2

The first part of the genome that was studied was the part that encodes for the spike proteins that give the family their distinctive crown-like appearance. All coronaviruses rely on spike proteins in order to infect other cells, but over time, each coronavirus has evolved these proteins differently, and this evolution is reflected in their genomes. In fact, the receptor-binding domain (RBD) in the spike protein is the most variable part of the coronavirus genome. Six RBD amino acids have been shown to be critical for binding to ACE2 receptors in their host cells, and so thus they also determine the host range of SARS-CoV-like viruses. Five of the six amino acids in SARS-Cov-2 differ from SARS-Cov, and existing computer models predicted that the new coronavirus would not bind to ACE2 as well as the SARS-cov virus. This provides the first piece of evidence: if a bioengineer was trying to design a coronavirus that threatened human health then surely they would use existing computer models to engineer a virus that bound better than a previously known virus? Dr Francis Collins, Director of the NIH, further backs this evidence with the statement that ‘any bioengineer trying to design a coronavirus that threatened human health probably would never have chosen this particular confirmation for a spike protein’.[2]

Actually, to their surprise the researchers found that the spike protein of the new coronavirus actually bound far better than computer predictions probably due to a previously unidentified alternate binding site. However, this alternate binding site is not incorporated into existing computer models and so therefore this would have not been considered if the virus was purposefully manipulated in a lab, as it would not have been known to be a target binding site.

The Overall Molecular Structure (Backbone) of Sars-cov-2

The analysis here showed that the backbone of the new coronavirus’s genome most closely resembles that of a bat coronavirus discovered after the pandemic began. However the region that binds ACE2 resembles a novel virus found in pangolins.

This provides a second piece of evidence that the coronavirus that causes Covid-19 almost certainly originated in nature. This backbone is not one seen before in other known viruses within the family. If a virus was to be engineered it would most likely be based on a backbone already known to cause serious diseases in humans, not a mix of two different ones.

Two Possible Scenarios of the Natural Origin of Sars-cov-2

At the end of their article, the researchers make clear that it is ‘improbable’ that SARS-CoV- 2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. Instead the researchers provide us with two possible scenarios that may explain how the novel coronavirus arose from a natural origin.

Natural Selection in an Animal Host Before Zoonotic Transfer

Many of the early cases of COVID-19 were linked to the Huanan market in Wuhan and so it is possible that an animal source was present at this location. And within this reservoir/host (currently suggested to be pangolins or bats due to the similarities to the viruses found in them[1]), the spike proteins in the virus mutated to bind to molecules similar in structure to the human ACE2 protein. This would therefore allow it to infect human cells.

This scenario fits with other recent outbreaks of coronavirus-caused disease in humans, with SARS arising from cat-like civets, and MERS arising from camels.[2]

Natural Selection in Humans Following Zoonotic Transfer

In this scenario, the virus crossed from animals into humans before it became capable of causing a human disease, and instead mutated gradually within the human. And so as a result of evolutionary changes over a long period of time, the virus eventually gained the ability to spread from human to human, as well as causing a serious human disease.

This scenario presumes that there was a period of unrecognised transmission in humans between the initial zoonotic event and the development of the adaptation to sustained transmission. This is essentially the case with MERS, where all human cases are the result of repeated jumps of the virus from camels to humans, producing single infections of short transmission chains that eventually resolve, as MERS has not adapted to sustained transmission.

A few studies have also been carried out to show low-level exposures to SARS-Cov-like coronaviruses in certain areas of China, however these studies could not distinguish whether the exposures were due to a specific virus. Therefore, further studies are needed to be conducted to determine the extent of prior human exposure to SARS-Cov-2.

Conclusion

Further studies into the genome and its similarities and differences to other coronaviruses are definitely needed in order to precisely say where SARS-Cov-2 arose from, but for now this research provides the evidence needed to prove that it indeed arose naturally, and is not the result of lab manipulation.

References

  1. Andersen, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C., & Garry, R. F. (2020). The proximal origin of SARS-CoV-2. Nature Medicine, 26(4), 450-452. doi:10.1038/s41591-020-0820-9
  2. Genomic Study Points to Natural Origin of COVID-19. (2020, March 26). Retrieved from https://directorsblog.nih.gov/2020/03/26/genomic-research-points-to-natural-origin-of-covid-19/

About the AuthorAbi Brooke is in sixth form studying for her A levels in the UK, looking to study Biochemistry at university. In her spare time, she’s a part of a dance team, and enjoys running. Genetics, Immunotherapy, and Virology are all fields she is interested in.

  1. Malayan Pangolins illegally imported into Guangdong province contain coronaviruses similar to SARS-Cov-2, and exhibit strong similarity to SARS-Cov-2 in the RBD, including six key RBD residues.

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