Evidence Summary

The receptor-binding domains (RBD) of the protein spike on the viral envelope has a high affinity for the ACE2 receptors of humans and several animal species. Five of the six RBD of SARS CoV-2 are similar to those of SARS CoV-1. 

However despite high affinity of the spike RBDs for the ACE2 receptors the fit is not perfect indicating that is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. The authors point to this as strong evidence that SARS-CoV-2 is not the product of man-made manipulation.

Another unique feature of CoV-2 is a cleavage site in the spike which could determine infectivity and virulence as happens in other respiratory viruses such as influenza. The authors propose three theories to explain the origins of the virus: 

1.Natural selection in an animal host before zoonotic transfer. 

However, no CoV so far found in animals is sufficiently similar to SARS CoV 2.

2. Natural selection in humans following zoonotic transfer. 

This presumes a period of unrecognised human to human transmission to allow the cleavage site to develop, from a common viral progenitor which jumped species and then adapted. 

3.Selection during passage in cells. 

Cleavage sites are acquired only after repeated passage in cell culture, this could also happen from cultures SARS Co-V 1. No lab escape episodes are known and the authors consider the genetic engineering hypothesis implausible.

None of these three hypotheses can be rejected or sustained on the basis of our current knowledge and further studies, especially of possible intermediate animal hosts, are required