- The evidence strongly suggests that SARS-CoV-2 is not a laboratory creation nor an intentionally manipulated virus. The RBD (receptor-binding domain) sequence of the SARS-CoV-2 spike protein appears to bind with high affinity to human ACE2, but this sequence is different than those predicted to be optimal for receptor binding based on previous computational analyses on SARS-CoV. Furthermore, the genetic data irrefutably indicates that SARS- CoV-2 is not derived from any previously isolated virus backbone.
- The high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2; this process occurred either in animal hosts before zoonotic transfer or in humans after zoonotic transfer, possibly even both. It is probable that bats served as reservoir hosts for the virus’ progenitor, as the closest coronavirus variant identified (which is 96% identical to SARS-CoV-2) was sampled in bats, but its spike protein diverges in the RBD sequence. Some pangolin coronaviruses exhibit strong similarity to SARS-CoV-2 in all the key RBD residues, hence the possibility of a recombinant virus, with the pangolin acting as an intermediate host. Because none of the bat or pangolin betacoronaviruses sampled thus far exhibit the characteristic polybasic cleavage sites of SARS-CoV-2, it is hypothesized that a zoonotic precursor of the virus jumped to humans, acquiring new genomic features through a final adaptation during undetected human-to-human transmission.
This genomic sequencing analysis, conducted by a team of scientists from Tulane, Scripps Research Institute, Columbia University, University of Edinburgh and University of Sydney, focuses on some of the novel SARS-CoV-2 coronavirus’ distinguishing genomic features to offer clues on its probable, as well as improbable, origins.
Andersen K.G., Rambaut A., Lipkin W.I., Holmes E.C., Garry R.F. (March 17, 2020). The proximal origin of SARS-CoV-2. Nature Medicine. https://doi.org/10.1038/s41591-020-0820-9