AsianScientist (Jun. 5, 2020) – With the world fighting an unseen enemy, the origins of SARS-CoV-2, the virus behind COVID-19, have understandably received intense scrutiny. In the absence of a clear answer, fringe theories regarding the virus supposed man-made origin have spread like wildfire. Though seemingly harmless, such theories create an atmosphere of fear, rumors and prejudice that jeopardise our global collaboration in the fight against this virus, as said by 27 international scientists in a strongly worded statement published in The Lancet. Misinformation has also harmed the reputation of distinguished scientists, such as Japanese Nobel laureate Tasuku Honjo, who was impersonated in a fake Twitter account that falsely claimed the virus was deliberately manipulated. Here, we examine the scientific evidence surrounding the origins of the coronavirus and spell out five reasons that support its natural origins.Its purported genetically engineered sequences are also found in other organisms
By the end of January, a sinister theory that SARS-CoV-2 was deliberately engineered from HIV made its way into the mainstream. The theory was traced back to a now-withdrawn preprint uploaded on bioRxiv.
Analyzing just four inserts in SARS-CoV-2s spike protein, the bioRxiv pre-print claimed that these inserts bore an uncanny resemblance to sequences also found in HIVs gp120 and Gag proteins. Because the sequences could not be found in other coronaviruses, the authors asserted that similarities were unlikely to be fortuitous, and that they may have been intentionally introduced into the virus.
But the truth is that the sequences the team looked at are so short that it is easy to find them just about anywhere. A quick run through the BLAST database, which compares nucleic acid and protein sequences, reveals that they can be found even in organisms like spiders (Araneus ventricosus) and the malaria parasite (Plasmodium malariae). In summary, the sequences are too short and too common to be significant.
Nature designed SARS-CoV-2 far better than humans ever could
To bolster evidence that the coronavirus evolved naturally, researchers turned to the spike proteinused by SARS-CoV-2 to bind to and penetrate the outer walls of its hosts cells. One notable feature they examined was the spike proteins receptor-binding domain (RBD), which helps the virus initially bind onto host cells.
Laboratory experiments have so far shown that SARS-CoV-2s RBD binds strongly to the host cells ACE2 receptor. And yet, computer simulations of the RBDs mutations predict that this shouldnt even be possible. In fact, the interaction is far from ideal; a different RBD mutation displays even better binding.
If the coronavirus was genetically engineered, then logic dictates that scientists would have chosen the best RBD mutation. However, in this scenario, it is clear that nature has outsmarted us allSARS-CoV-2 has evolved to be far better than humans could have ever imagined.
As they say, the proof is in the pudding. Or in this case, the spike protein.
Its evolutionary history tells us so
Compared to common laboratory coronavirus strains, SARS-CoV-2s evolutionary tree shows that it is more closely related to coronaviruses isolated from wild bats and pangolins. The bat coronavirus RaTG13, for instance, shares about 96 percent of its genome with SARS-CoV-2. Given their similarities, theres been speculation that the novel coronavirus couldve been derived from RaTG13.
Though a genetic difference of four percent seems small, its huge in evolutionary terms. According to virologist Edward Holmes from the University of Sydney, this divergence is equivalent to an average of 50 years of evolutionary change. Generating SARS-CoV-2 in the laboratory would require a progenitor virus with even greater genetic similaritycertainly not one with half a centurys worth of divergence!
Mutations in SARS-CoV-2s RBD are also nearly identical to those found in pangolin coronaviruses, and not RaTG13. This provides stronger evidence that SARS-CoV-2 likely made the jump from bats to humans through a pangolin intermediate, instead of having been created in a laboratory.
Experimental tools to engineer such a virus do not exist
SARS-CoV-2s spike protein has two other features that suggest its natural origin: the cleavage site and O-linked glycans. Its cleavage site allows the coronavirus to open and enter host cells, while glycans help shield it from antibodies.
While viruses could evolve cleavage sites in laboratory conditions over long periods of time, it is just not possible for SARS-CoV-2s O-linked glycan to have developed under a typical cell-culture setting. Developing the glycan shield requires evolutionary pressure from an intact immune system, which cells in petri dishes obviously lack.
Could the coronavirus have been created in animal models, then? Fortunately, there are no known animal models that could have allowed SARS-CoV-2s spike protein to develop both a glycan shield and a high affinity for the human ACE2 receptor. Therefore, SARS-CoV-2 could not have been created in a laboratory because the tools we have at the moment are inadequate for doing so.
It is highly unlikely the virus escaped from a lab
Whispers that the virus supposedly escaped from the laboratory date back to a preprint uploaded to ResearchGate in early February. Providing only the flimsiest of evidence to substantiate their claim, the authors cited the close proximity of the Wuhan Centers for Disease Control & Prevention and the Wuhan Institute of Virology (WIV) to the Huanan Wholesale Seafood Market, once considered as the outbreaks ground zero.
As the WIV was known to study bat coronaviruses, the authors suggest that the outbreak could have begun as a laboratory mishap. However, none of the COVID-19 patient samples match the coronavirus strains they had taken from bat caves, said Professor Shi Zhengli, head of the laboratory studying bat coronaviruses at WIV.
Since then, scientists around the world have voiced their support for the WIVs high standards for biocontainment.
I have worked in this exact laboratory at various times for the past two years. I can personally attest to the strict control and containment measures implemented while working there, stated Assistant Professor Danielle Anderson, scientific director of Duke-NUS Medical Schools Animal Biosafety Level-3 laboratory, in a review on Health Feedback.
As compelling evidence against the man-made virus theory mounts, it is worth noting that there hasnt been any viable counterclaim against SARS-CoV-2s natural origin so far. With all the uncertainty surrounding the virus, applying Occams razor is surely prudent in this scenario. The simplest explanation is likely the best one: the virus is not man-made.
Copyright: Asian Scientist Magazine.Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.