Although much is already known about the SARS-CoV-2 coronavirus which causes Covid-19 disease, one of the remaining challenges is to clarify its origin. There have been so many rumours and hypotheses that the general public has reason to be confused: did the outbreak occur in a market in Wuhan or elsewhere? Is the virus really new? Did it jump to humans from bats or pangolins? Did it escape from a laboratory? Even more intriguing, could it be a biological weapon created by China, or by the US against China?
It is important to keep in mind what science can and cannot prove. Even if all the scientific evidence points to the virus being a mere product of nature, there is no way to disprove that it was deliberately constructed to appear natural. Experts point out that the logic of conspiracy theories is based on the fact that they are, in themselves, irrefutable. Thus, it is impossible to disprove with evidence that SARS-CoV-2 is a natural virus that has escaped from a laboratory. The only antidote to these ideas is rational thought—the burden of proof lies with those who defend such suppositions.
The conspiracy theories surrounding the coronavirus revolve around a study from 2015. A team of researchers led by the University of North Carolina published in Nature Medicine the modification of a coronavirus of the Severe Acute Respiratory Syndrome (SARS) adapted to mice whose Spike (S) protein, the key the virus uses to infect cells, had been replaced by its equivalent from a Chinese bat coronavirus called SHC014. The resulting chimeric virus had pathogenic potential for humans, which is why the study received serious criticism. The project involved scientists from the Wuhan Institute of Virology, one of two centres in Wuhan working with bat coronaviruses.
Epidemiological and genetic data of the virus
In addition, in February 2020, a brief, purely speculative article appeared —not a study, as has sometimes been implied— in which two Chinese researchers ventured into the possible origin of the SARS-CoV-2 virus being a laboratory in Wuhan. The rumours escalated into yet another source of US-China rivalry. While President Donald Trump insists on referring to the coronavirus as the “Chinese virus,” other political figures in the United States have encouraged the rumour about the creation of the pathogen in a laboratory. In turn, officials in the Asian giant have counterattacked by accusing the US of having created and released the virus in Wuhan.
But to date, there is absolutely no proof of any of this. The scientific community, the only source that provides solid and verifiable evidence, has left it up to the pathogen itself to tell its story through its epidemiological and genetic data. With regard to the former, it has not yet been possible to confirm whether the outbreak occurred in the Huanan seafood market in Wuhan or whether it was amplified there after appearing elsewhere.
But if there are still doubts about the where, there does not seem to be any about the when, thanks to the genetic data. The comparison of the viral genomes obtained over time serves as a molecular clock to determine the approximate time at which the pathogen appeared. These studies have placed the first infection between mid-November and early December 2019, in line with the Chinese government’s estimate that the first infected person contracted the virus on 17 November in Hubei Province. “Our data effectively rule out the scenario that the virus circulated in humans for a long time before that,” said the head of one such study, Tanja Stadler of the Zurich Federal Institute of Technology in Basel, Switzerland.
Genomic analyses do not suggest any other origin for the coronavirus but the natural one. In the journal Nature Medicine, a study led by researcher Kristian Andersen at Scripps Research has scrutinized the pathogen’s RNA, reaching several conclusions. First, there is no genetic evidence that the virus was built with any of the known systems of genetic engineering for coronaviruses, such as that used to generate the chimeric virus of 2015. “By comparing the available genome sequence data for known coronavirus strains, we can firmly determine that SARS-CoV-2 originated through natural processes,” Andersen concludes.
The study focused on two key features of the S-protein: its region of binding to the cell receptor (Receptor Binding Domain, RBD), called ACE2, and a sequence that allows the cutting of the S-protein by a cell enzyme called furan, which increases its infectivity. As for the RBD, whose affinity for binding to ACE2 is much higher than that of the SARS virus, its makeup is nevertheless not the optimal one that computational calculations would have advised; natural selection has found a solution as unpredictable as it is effective.
A virus originated in wildlife
The furan-cutting site is still an unknown; in viruses such as influenza or HIV these sequences are associated with a high pathogenic potential, but are not present in the coronaviruses closest to SARS-CoV-2. According to Andersen and his collaborators, it is not yet known whether the virus acquired all its current traits before or after jumping from an animal to humans. But the scientific consensus is nevertheless clear. As an open letter published in The Lancet signed by 27 experts stated, all studies “overwhelmingly conclude that this coronavirus originated in wildlife, as have so many other emerging pathogens.”
As for the identity of the animal hosts, there are still some loose ends to be tied up. SARS-CoV-2 is very similar to other bat and pangolin coronaviruses. One of the first published genetic sequences of the virus revealed it to be 96% identical to a bat coronavirus called RaTG13, indicating that these animals could be the original reservoir. However, there are no documented cases of direct transmission from bats to humans, and the similarity between the S-protein sequences is relatively low.
Coronaviruses with less overall genetic similarity to SARS-CoV-2 than RaTG13 have been found in pangolins, but their RBDs are almost identical to that of the human virus. The director of one such study, Zhigang Zhang of Yunnan University (China), explains that his results “support pangolins as one of potential original reservoirs but not as intermediate hosts of SARS-CoV-2. Indeed, for RBD of virus spike protein, possible recombinations occurred between pangolin-CoV and Bat RaTG13.” However, Zhang acknowledges that this does not clarify the origin of the furan-cutting site, which is absent in pangolin viruses and RaTG13; the animal source of the virus remains an open question.