The novel Corona Virus SARS-CoV-2 has been affecting everyone on a global scale

one way or another. Because of this, I have decided to read the paper “The
proximal origin of SARS-CoV-2 by Kristian Andersen, Andrew Rambaut, W. Lipkin,
Edward Homes and Robert Garry who published this article in Nature Medicine the
17th of March of 2020. This article presents their findings from studying the SARS-
CoV-2 viruses’ genome and the biochemical predictions based on predicted and
known protein structures of this virus to understand its new novel features and its
possible origins.

Eukaryotic viruses and the Novel Corona virus SARS-CoV-2

Eukaryotic viruses infect eukaryotes like fungi, and animals, plants. The new corona
virus is surrounded by a membrane with proteins called spike proteins that interact
with eukaryotic cell receptors. This interaction tricks the cell into allowing the virus
to enter the cell and begin to multiply. Notable features of SARS-CoV-2 are found on
the Spike proteins. Part of the spike protein acts as a receptor that can interact
with the human AEC2 receptor. Additionally, the spike protein has a new physical
characteristic that allows it to be cleaved by proteases, enzymes that break apart
proteins. This cleavage site, called a polybasic cleavage site, has not been seen in
corona-like viruses before. The spike protein is also predicted to have a O-linked
glycans that influence how the protein behaves. At this time, it has not been
confirmed that O-linked glycans are present and if they are, what their effects on
the severity of viral infections and the ease of spread is[ CITATION And20 \l 1033 ].

Investigating common ancestors of SARS-CoV-2

Through comparing the viral genome to the genomes of other corona viruses, it has
been determined that bat corona-like viruses are most similar in their genetic
sequence. This indicates that bat corona-like viruses are a likely the most recent
known common viral ancestor to the novel corona virus SARS-CoV-2. Bat corona-like
viruses can bind to the AEC2 receptor on humans but lack the O-linked glycans and
cleavage site on the spike protein. Another contender for a possible predecessor of
SARS-CoV-2 virus is the corona-like viruses in Malayan pangolins (Manis javanica)
that have O-linked glycans in their spike proteins but are not able to bind to AEC2
receptors in humans (Andersen, et.al, 2020).
Looking at the genetic evidence

Image from [ CITATION And20 \l 1033 ].

The top blue line in this image represents viral genome. The salmon collored bar is
the spike protein. This spike protein has to distinct regions called S1 subunit and S2
subunit. For each subunit, the human SARS-CoV-2 is compared to the Bat RaTG13
viral genome, the Pangolin corona-like virus, sections are compared across the
SARS-CoV viral genome and two Bat SARS-CoV-related viral genomes. These are the
genome that were identified as being related to the novel Corona virus due to
similarity between genome sequences. Each of the amino acids that makes up the
protein is color coded. The amino acids that are of interest are highlighted with a
blue box. Amino acids that are highly conserved are observed in all genomes. The
dashed lines help the genomes remained aligned when amino acids are not present.
This can signify that a amino acid was added to the genome, or an amino acid was
deleted.
The Receptor-binding domain ACE2 contact residues is the part of the spike protein
that interacts with the ACE2 receptor in human cells. Many of the amino acids are
highly conserved across all viral genomes shown. Some amino acids like the
Leucine (pink) is unique to three viruses, SARS-CoV-2, Bat RaTG13 and pangolin, the
two possible ancestors of SARS-CoV-2. In the novel cleavage site called the
polybasic cleavage site is not seen in any of the viral genomes. These two cites are
of interest of study since they relate to how easily the viruses can infect our cells,
and thus how easy it is to transmit the virus.

Could this virus been manufactured?

President Trump has continually claimed that the chines government intentionally
manufactured this virus. If SARS-CoV-2 had been manufactured to specifically infect
humans using the AEC2 receptor, it would be predicted that the spike proteins
would perfectly bind to these receptors. While SARS-CoV-2 binds very well to the
human AEC2 receptor, the interaction between the spike protein and the receptor is
not perfect, suggesting that this interaction could be improved (Andersen, et.al,
2020). This suggests that the interaction between the spike protein and the human
receptor was developed through natural selection. Additionally, the novel feature of
the cleavage cite on the spike proteins is only known to have arisen form viral
interactions with immune systems. Making the likelihood that this virus accidentally
escaped from a lab also highly unlikely.

As a result, the most likely mode this virus came about was through natural
selection and was able to be transmitted from the animal host (most likely bats or
pangolins) to humans. At this time it is unclear if the virus made a direct jump from
the animal host to humans or if the virus jumped back and forth from human to
animal host several times as it developed better mechanisms to infect humans
(Andersen, et.al , 2020).

Understanding how this virus arose, will give us more information to be able to
predict if the current SARS-CoV-2 will continue to adapt in humans and become a
constant threat like the flu or common cold or if the occurrence of SARS-CoV-2
viruses are more rare. Additionally, understanding the source of the virus can help
us humans develop better regulations around interacting with wildlife such as bats
and pangolins to minimize the risk of creating another zoonotic virus.
Let me know your thoughts in the comments about how SARS-CoV-2 has affected
you and what you think about this article.

If you want to read the paper yourself, you can check out the article below.
https://doi.org/10.1038/s41591-020-0820-9

References
Andersen, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C., & Garry, R. F. (2020,
March 17). The Proximal Origin of SARS-COV-2. Nature Medicine(26), pp. 450-
452. doi:https://doi.org/10.1038/s41591-020-0820-9