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Two hypotheses of the origin of SARS-CoV-2 exist: • A spillover from an animal host somewhere outside a laboratory • A laboratory-related accident • Finding features within the genome to address these hypotheses would advance the investigation without requiring the cooperation of third-parties • Previous analyses of the unprecedented, first ever furin cleavage site in a sarbecovirus and the exceptional pre-adaption of the receptor binding domain to human ACE2 have been challenged because they provide an evolutionary advantage to the virus and, no matter how seemingly unnatural, as supporting a natural process • Here I perform an analysis of the number, location, genome pattern, and sequences of two restriction sites, BsaI and BsmBI, that helps distinguish natural viruses from synthetic viruses • These two Type IIS restriction enzymes are the workhorses of synthetic coronavirus research and part of Baric’s “No See ‘Em” technology • An advantage of this analytical approach is that, in synthetic biology, the manipulation of these small, six nt sequences is the foundation of reverse genetics but their small size and random location within a genome, unrelated to genes, makes it extremely unlikely that they could provide an evolutionary advantage • Finding multiple patterns within SARS-CoV-2's genome to be both a) consistent with man-made chimeric virus genomes and b) demonstrably extremely inconsistent with all observed natural sarbecovirus genomes, greatly advances the investigation of COVID-19's origins. This version 2 corrects some minor typographical errors without changing the conclusions of the analysis. The conclusion of this analysis is that SARS-CoV-2 has the hallmarks of a laboratory-constructed synthetic virus.
SARS-CoV-2 synthetic virus infectious clone Wuhan Institute of Virology
SARS-CoV-2 synthetic virus infectious clone Wuhan Institute of Virology