An open debate on SARS-CoV-2’s proximal origin is long overdue

"Conclusion: More than a year after the initial documented cases in Wuhan, the source of SARS-CoV-2 has yet to be identified and the search for a direct or intermediate host in nature has been so far unsuccessful. The low binding affinity of SARS-CoV-2 to bat ACE2 [angiotensin-converting enzyme 2] studied to date, does not support Chiroptera as a direct zoonotic agent. Furthermore, the reliance on pangolin CoV RBD [receptor binding domain] similarity to SARS-CoV-2 as evidence for natural zoonotic spillover is flawed as pangolins are unlikely to play a role in SARS-CoV-2’s origin and recombination is not supported by recent analysis. At the same time, genomic analyses pointed out that SARS-CoV-2 exhibits multiple peculiar characteristics not found in other Sarbecoviruses. A novel multibasic FCS [furin cleavage site] confers numerous pathogenetically advantageous capabilities, the existence of which is difficult to explain though natural evolution; SARS-CoV-2 to hACE2 binding is far stronger than SARS CoV, yet there is no indication of amount of evolutionary adaptation that SARS-CoV or MERS CoV underwent. The flat topography of the GBD [ganglioside-binding domain] in the NTD [N terminal domain] of SARS-CoV-2 does not conform with typical host evasion evolutionary measures exhibited by other human CoVs. The combination of peptide mimicry to humans and mice, physical structure and binding strength, as well as high adaptation for human infection and transmission from the earliest strains, might suggest the use of humanized mice for the development of SARS-CoV-2 in a laboratory environment. The application of mouse strains expressing hACE2 for SARS-CoV related research is well documented.. Additionally, culturing and adapting CoVs to different cell lines, including human airway epithelial cells has been experimentally conducted in various laboratories. While a natural origin is still possible and the search for a potential host in nature should continue, the amount of peculiar genetic features identified in SARS-CoV-2’s genome does not rule out a possible gain-of-function origin, which should be therefore discussed in an open scientific debate."