The Proximal Origin of SARS-CoV-2

[fuyutao]

@arambaut

For a precursor virus to acquire the polybasic cleavage site and mutations in the spike protein suitable for human ACE2 receptor binding, an animal host would likely have to have a high population density – to allow natural selection to proceed efficiently – and an ACE2 gene that is similar to the human orthologue.

There is one animal species meeting these 3 criteria:

1. The species is common with a high population density, some running in the wild;
2. BLASTing the short SARS-CoV-2 furin cleavage site PRRARS against coronavirus, there is only one species ranked above bat, and the hit is also in spike protein;
3. In a peer reviewed article (https://onlinelibrary.wiley.com/doi/10.1002/jmv.25726), the species’ key ACE2 amino acids are closer to human than between pangolin and human. Another paper in preprint (https://www.researchgate.net/publication/339741547_Predicting_the_Angiotensin_Converting_Enzyme_2_ACE2_Utilizing_Capability_as_the_Receptor_of_SARS-CoV-2) predicts the species’ ACE2 can bind SARS-CoV-2.