Fact Check: 5 Reasons Why The Coronavirus Is Not ‘Man-made’

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 The theory was traced back to a now-withdrawn preprint uploaded on bioRxiv.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-2’s spike protein, the bioRxiv pre-print claimed that these inserts bore an “uncanny” resemblance to sequences also found in HIV’s 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.

To bolster evidence that the coronavirus evolved naturally, researchers turned to the spike protein—used by SARS-CoV-2 to bind to and penetrate the outer walls of its host’s cells. One notable feature they examined was the spike protein’s receptor-binding domain (RBD), which helps the virus initially bind onto host cells.

Laboratory experiments have so far shown that SARS-CoV-2’s RBD binds strongly to the host cell’s ACE2 receptor. And yet, computer simulations of the RBD’s mutations predict that this shouldn’t 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 all—SARS-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.

Compared to common laboratory coronavirus strains, SARS-CoV-2’s 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, there’s been speculation that the novel coronavirus could’ve been derived from RaTG13.

Though a genetic difference of four percent seems small, it’s 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 similarity—certainly not one with half a century’s worth of divergence!

Mutations in SARS-CoV-2’s 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.

SARS-CoV-2’s 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-2’s 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-2’s 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.

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 outbreak’s 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 WIV’s 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 School’s 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 hasn’t been any viable counterclaim against SARS-CoV-2’s natural origin so far. With all the uncertainty surrounding the virus, applying Occam’s razor is surely prudent in this scenario. The simplest explanation is likely the best one: the virus is not man-made.