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Origins of SARS-CoV-2

Written by JuWon Park

Prior to a White House press briefing on April 30th, the Office of the Director of National Intelligence released a statement that rejected conspiracy theories about the virus being a bioweapon, concluding that the virus was “not man-made or genetically modified” (Rincon, 2020). Later that day, Trump stated that he has a high degree of confidence that the Wuhan Institute of Virology was the origin of the virus and accused the World Health Organization (WHO) for acting “like the public relations agency for China” (Beaumont, 2020). 

On March 17, Nature Medicine published research that showed the SARS-CoV-2 virus (which causes COVID-19) was a result of natural selection (Andersen et al., 2020). Using the sequenced genome made available by Chinese scientists, the authors analyzed the receptor-binding domain (RBD) and the cleavage site, both of which determine how a virus can grab and enter host cells (“COVID-19 coronavirus epidemic has a natural origin”, 2020). 

There are currently three known highly pathogenic human coronaviruses: the Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 2012, severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, and the 2019 novel coronavirus (2019-nCoV) (“COVID-19 coronavirus epidemic has a natural origin”, 2020).

The study identified two mutations in the RBD and spike protein that compares SARS-CoV-2 from other coronaviruses (Andersen et al., 2020). 

Both SARS-CoV and SARS-CoV-2 S proteins bind to ACE2. SARS-CoV-2’s RBD, which is like a hook that clings to host cells, has a high attraction to human angiotensin-converting enzyme 2 (ACE2), which regulates blood pressure. ACE2 expression has previously been shown to correlate with the infection of the human airway by severe acute respiratory syndrome (SARS)  coronavirus (Jia et al., 2005). Five out of six RBD amino acids critical for ACE2 receptor binding are different between the SARS-CoV and SARS-CoV-2, as SARS-CoV-2 shows a higher binding affinity with human ACE2 receptors (Andersen et al., 2020). This difference, in addition to computational analyses, help us predict that the SARS-CoV-2 spike protein resulted from natural selection for optimal binding, which eliminates the possibility of manipulation (Andersen et al., 2020). 

The backbone (or molecular structure) of SARS-CoV-2 has unique features such as the polybasic cleavage site (RRAR) and the addition of O-linked glycans. The functional purpose of these features has not yet been determined but is hypothesized to enhance infection of human cells and immunoevasion (evading the immune system) (Andersen et al., 2020).

Bats could also be reservoir hosts (living hosts for a species) for SARS-CoV-2 because of the similarity between SARS-CoV-2 and bat SARS-CoV-like coronaviruses. However, neither bat nor pangolin beta coronaviruses have yet been found with polybasic cleavage sites. There also exists the possibility of the insertion of the RRAR during human-to-human transmission (Andersen et al., 2020).

The acquisition of the unique features of SARS-CoV-2 through cell culture or animal passage is highly unlikely because there doesn’t exist a known coronavirus similar to this with high genetic similarity (Andersen et al., 2020).  

Despite the scientific reasoning surrounding the origins of SARS-CoV-2, there still exist political tensions regarding this topic. This article attempts to clarify the specific technicalities to explain the improbability of conspiracy theories that blame one party, which causes distrust and hate.



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

Beaumont, P. (2020, May 01). Where did Covid-19 come from? What we know about its origins. Retrieved from

COVID-19 coronavirus epidemic has a natural origin. (2020, March 17). Retrieved from

Coronavirus: Trump stands by China lab origin theory for virus. (2020, May 01). Retrieved from

Jia, H. P., Look, D. C., Shi, L., Hickey, M., Pewe, L., Netland, J., . . . Mccray, P. B. (2005). ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human Airway Epithelia. Journal of Virology, 79(23), 14614-14621. doi:10.1128/jvi.79.23.14614-14621.2005

Rincon, P. (2020, May 01). Coronavirus: Is there any evidence for lab release theory? Retrieved from, W., He, L., Zhang, X., Pu, J., Voronin, D., Jiang, S., . . . Du, L. (2020). Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: Implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cellular & Molecular Immunology,17(6), 613-620. doi:10.1038/s41423-020-0400-4

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