The origin of SARS-CoV-2 is still hotly debated

Since the first cases of COVID-19 in December 2019 in Wuhan, we have been trying to establish the origins of SARS-CoV-2. Currently, several hypotheses are being debated.   

• Firstly, did SARS-CoV-2 emerge from an animal reservoir (zoonosis)?

A large majority of human viruses do, in effect, emerge from animal sources. Coronaviruses infect numerous species, including humans, and four of them are endemic (HCoV-OC43, HCoV-HKU1, HCoV-229E, HCoV-NL63). Although the ancestor of SARS-CoV-2 and its reservoir have not yet been formally identified, very close viral strains (with more than 96% genetic identity in the case of RaTG13) have been found in bats and other species (pangolins, civets, raccoon dogs), in particular in certain rural provinces of Asia (Yunnan). Epidemiological data has localised the epicentre of the pandemic in Wuhan, where some of these types of animal were reportedly found in Huanan market. It is probable that other localities were involved and that repeated contact was necessary for the epidemic to get a foothold. Previous human coronavirus infections, including SARS-CoV, have involved similar scenarios.

• Secondly, was SARS-CoV-2 able to escape from a laboratory ?

Such a scenario has already been responsible for several infections in the past, but they have been very quickly brought under control. The only documented epidemic arising from human error was the H1N1 flu outbreak of 1977, following large-scale vaccine trials. Today, no data exists to show that the Wuhan Institute of Virology (WIV), or any other laboratory, was involved in a study of SARS-CoV-2 or another possible ancestor before the outbreak of the pandemic. Amongst laboratory personnel, there were no reports of cases of COVID-19 or HIV. Nor would the lab scenario explain the multiple hospitalisations that occurred before December 2019. The three strains of infectious coronavirus studied at the WIV were close to SARS-CoV and not SARS-CoV-2.

In addition, the culture techniques in use there induce the loss of the furin cleavage site, an essential step for SARS-CoV-2 infection. Studies carried out at the WIV also did not use any closely related viral genome. Mice, the animal model most often used to study the virus, cannot be naturally infected by SARS-CoV-2, and no genetic trace of adaptation to this animal have been found.

• Thirdly, was SARS-CoV-2 genetically engineered or adapted in the laboratory so as to develop a strain that could infect humans?

Several mutations, occurring independently in the current “variants of concern”, increase the virus’ contagiousness by optimising its binding to the ACE2 human receptor. These mutations seem to be indispensable for the virus to be able to adapt to humans, but were absent in the Wuhan ancestral strain. Furthermore, some natural strains found in pangolins bind more efficiently to ACE2 than SARS-CoV-2. All this rules out the hypothesis of the virus causing the pandemic having been “pre-adaptated” in the laboratory. In the strains closest to SARS-CoV-2, the furin cleavage site is absent, and this has also fed theories of human intervention. But genetic signatures show that it is more likely that this site was acquired by recombination (a natural evolutionary mechanism involving exchange of genetic material) from another strain (HKU9-1). In addition, this cleavage site (R-R-A-R) is less effective than the canonical or general site (R-X-R/K-R), and no evidence of molecular engineering activity of this type has been found at the WIV.

• Finally, no concrete proof exists at the current time to indicate that the virus came from a laboratory, while evidence of natural zoonosis continues to grow.

These theories appeared because the WIV was studying, by chance, a number of coronaviruses at the time of the virus’ emergence. In addition, Wuhan is a densely populated city, with connections to many other cities through travel and commerce, at both national and international levels, and it hosts several animal markets. All of this created conditions favourable to the emergence of a coronavirus. Inaccurate interpretations and poor understanding of the origins of zoonoses are in part due to an absence of collaborative research, and we will be exposed to other viral episodes if we continue to commit the same errors.