On Saturday we reported that Dr. Li-Meng Yan - a Chinese virologist (MD, PhD) who fled the country, leaving her job at a prestigious Hong Kong university - appeared last week on British television where she claimed SARS-CoV-2, the virus which causes COVID-19, was created by Chinese scientists in a lab.
On Sunday, Li-Meng joined Twitter - and on Monday, just hours ago, she tweeted a link to a paper she co-authored with three other Chinese scientists titled:
Unusual Features of the SARS-CoV-2 Genome Suggesting Sophisticated Laboratory Modification Rather Than Natural Evolution and Delineation of Its Probable Synthetic Route
"The evidence shows that SARS-CoV-2 should be a laboratory product created by using bat coronaviruses ZC45 and/or ZXC21 as a template and/or backbone. Building upon the evidence, we further postulate a synthetic route for SARS-CoV-2, demonstrating that the laboratory-creation of this coronavirus is convenient and can be accomplished in approximately six months.
THE SMOKING GUN:
Given that RBM fully dictates hACE2-binding and that the SARS RBM-hACE2 binding was fully characterized by high-resolution structures (Figure 3)37,38, this RBM-only swap would not be any riskier than the full Spike swap. In fact, the feasibility of this RBM-swap strategy has been proven. In 2008, Dr. Zhengli Shi’s group swapped a SARS RBM into the Spike proteins of several SARS-like bat coronaviruses after introducing a restriction site into a codon-optimized spike gene (Figure 5C). They then validated the binding of the resulted chimeric Spike proteins with hACE2. Furthermore, in a recent publication, the RBM of SARS-CoV-2 was swapped into the receptor-binding domain (RBD) of SARSCoV, resulting in a chimeric RBD fully functional in binding hACE2 (Figure 5C)39. Strikingly, in both cases, the manipulated RBM segments resemble almost exactly the RBM defined by the positions of the EcoRI and BstEII sites (Figure 5C). Although cloning details are lacking in both publications39,47, it is conceivable that the actual restriction sites may vary depending on the spike gene receiving the RBM insertion as well as the convenience in introducing unique restriction site(s) in regions of interest. It is noteworthy that the corresponding author of this recent publication, Dr. Fang Li, has been an active collaborator of Dr. Zhengli Shi since 201049-53. Dr. Li was the first person in the world to have structurally elucidated the binding between SARS-CoV RBD and hACE238 and has been the leading expert in the structural understanding of Spike-ACE2 interactions. The striking finding of EcoRI and BstEII restriction sites at either end of the SARS-CoV-2 RBM, respectively, and the fact that the same RBM region has been swapped both by Dr. Shi and by her long-term collaborator, respectively, using restriction enzyme digestion methods are unlikely a coincidence. Rather, it is the smoking gun proving that the RBM/Spike of SARS-CoV-2 is a product of genetic manipulation."
Chinese scientists then presciently tried to cover their tracks:
Although it may be convenient to copy the exact sequence of SARS RBM, it would be too clear a sign of artificial design and manipulation. The more deceiving approach would be to change a few nonessential residues, while preserving the ones critical for binding. This design could be well-guided by the high-resolution structures (Figure 3)37,38. This way, when the overall sequence of the RBM would appear to be more distinct from that of the SARS RBM, the hACE2-binding ability would be well-preserved. We believe that all of the crucial residues (residues labeled with red sticks in Figure 4, which are the same residues shown in sticks in Figure 3C) should have been “kept”. As described earlier, while some should be direct preservation, some should have been switched to residues with similar properties, which would not disrupt hACE2-binding and may even strengthen the association further [ZH: i.e., the virus was weaponized and enchanced]. Importantly, changes might have been made intentionally at non-essential sites, making it less like a “copy and paste” of the SARS RBM.