For anyone who believes that the pandemic was a "natural zoonotic spillover," please read the following sections of the DEFUSE proposal, highlight copied below:<p>"Synthesis of Chimeric NovelSARS-CoVQS: We will commercially synthesize SARSr-
Cov glycoprotein genes, designed for insertion into SHCO14 or WIV16 molecular clone backbones (88% and 97% S-protein identity to epidemic SARS-Urbani. These are BSL-3, not select agents or subject to P3CO (they use bat SARS-CoV backbones which are exempt) and are pathogenic to hACE2 transgenic mice. Different backbone strains increase recovery of viable:viruses identification of barriers for RNA recombination-mediated gene transfer between strains™. Recombinant viruses will be recovered in Vero cels, or in mouse cells over-expressing human, bat or civet ACE2 receptors to support cultivation ofviruses with a weaker RBD-human ACE2 interface. "<p>In vitro testing of chimeric viruses: All chimeric viruses will be sequence verified and evaluated for. i) ACE2 receptor usage across species in vitro, ii) growth in primary HAE, iii) sensitivity to broadly cross neutralizing human monoclonal antibodies that recognize unique epitopes in the RBD. Should some isolates prove highly resistant to our mAB panel we will evaluate cross neutalzation against a cited number of human SARS-CoV serum samples from the Toronto outbreak. Chimeric viruses that encode novel genes with slower potential will be used to identify SARSr-CoV strains for recovery as full genome length viable viruses.<p>In vivo pathogenesis: Groups of 10 animals will be infected intranasally with 1.0 x 106 PFU of each vSARSr-CoV, clinical signs (weight loss, respiratory function, mortality, et) followed for 6 days..."<p>S2 Proteolytic Cleavage and Glycosylation Sites:
... We will analyze all SARS-CoV S gene sequences for appropriately conserved proteolytic cleavage sites in S2 and for the presence of potential furin cleavage sites".... Where clear mismatches occur, WE WILL INTRODUCE APPROPRIATE HUMAN SPECIF CLEAVAGE SITES AND EVALUATE GROWTH POTENTIAL IN VERO CELL AND HAE CULTURES."<p>I apologize as the copy and paste from a PDF is not ideal. If anyone ever wanted a smoking gun, this is it. The WIV proposed to build SARS-COV2 in 2018/2019. The key point is that when someone proposes this type of research, they often have already done the work and the funding will be used to generate the next result needed for future funding.<p>Also, one item that the world conveniently forgot was that half of the specialists in this field believed passionately that the only way to prevent the next Pandemic was to create super viruses in the lab (this is in the public record). Given the extensive history of lab leaks and suspected lab leaks, this path is absolute and complete hubris and folly. The same folks who were pushing this agenda (and the DEFUSE proposal is filled with little notes as to how certain rules could be skirted) were the folks who immediately claimed that it was absolutely impossible for this to be a lab leak.<p>This proposal was shopped to a number of different US agencies in 2019. This means that there were likely dozens of individuals in multiple agencies who reviewed this proposal and said absolutely nothing when the pandemic broke.