Updated analysis to reject the laboratory-engineering hypothesis of SARS-CoV-2

A clear understanding of the origin of SARS-CoV-2 is important for future pandemic preparedness. Here, I provided an updated analysis of the type IIS endonuclease maps in genomes of alphacoronavirus, betacoronavirus, and SARS-CoV-2. Scenarios to engineer SARS-CoV-2 in the laboratory and the associated workload was also discussed. The analysis clearly shows that the endonuclease fingerprint does not indicate a synthetic origin of SARS-CoV-2 and engineering a SARS-CoV-2 virus in the laboratory is extremely challenging both scientifically and financially. On the contrary, current scientific evidence does support the animal origin of SARS-CoV-2. •The pattern of BsmBI/BsaI restriction sites is highly diverse in coronaviruses.•Endonuclease fingerprint does not indicate a synthetic origin of SARS-CoV-2.•Creating a SARS-CoV-2 virus in the laboratory is extremely challenging in practice.