1.3 …. The evidence collectively suggests that the furin-cleavage site in the SARS-CoV-2 Spike protein may not have come from nature and could be the result of genetic manipulation. The purpose of this manipulation could have been to assess any potential enhancement of the infectivity and pathogenicity of the laboratory-made coronavirus. Indeed, recent studies have confirmed that the furin-cleavage site does confer significant pathogenic advantages to SARS-CoV-2.
1.4 Summary
Evidence presented in this part reveals that certain aspects of the SARS-CoV-2 genome are extremely difficult to reconcile to being a result of natural evolution. The alternative theory we suggest is that the virus may have been created by using ZC45/ZXC21 bat coronavirus(es) as the backbone and/or template.The Spike protein, especially the RBM within it, could have been artificially manipulated, upon which the virus has acquired the ability to bind hACE2 and infect humans. This is supported by the finding of a unique restriction enzyme digestion site at either end of the RBM. An unusual furin-cleavage site may have been introduced and inserted at the S1/S2 junction of the Spike protein, which contributes to the increased virulence and pathogenicity of the virus.
These transformations have then staged the SARSCoV-2 virus to eventually become a highly-transmissible, onset-hidden, lethal, sequelae-unclear, and massively disruptive pathogen.Evidently, the possibility that SARS-CoV-2 could have been created through gain-of-function manipulations at the WIV is significant and should be investigated thoroughly and independently.
2. Delineation of a synthetic route of SARS-CoV-2
In the second part of this report, we have described a synthetic route of creating SARS-CoV-2 in a laboratory setting. It is postulated based on substantial literature support as well as genetic evidence present in the SARS-CoV-2 genome. Although steps presented herein should not be viewed as exactly those taken, we believe that key processes should not be much different. Importantly, our work here should serve as a demonstration of how SARS-CoV-2 can be designed and created conveniently in research laboratories by following proven concepts and using well-established techniques.
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Importantly, research labs, both in Hong Kong and in mainland China, are leading the world in coronavirus research, both in terms of resources and on the research outputs. The latter is evidenced not only by the large number of publications that they have produced over the past two decades but also by their milestone achievements in the field:
They were the first to identify civets as the intermediate host for SARS-CoV and isolated the first strain of the virus71;
They were the first to uncover that SARS-CoV originated from bats; they revealed for the first time the antibody-dependent enhancement (ADE) of SART-CoV infections;
They have contributed significantly in understanding MERS in all domains (zoonosis, virology, and clinical studies)75-79; they made several breakthroughs in SARS-CoV-2 research.
Last but not least, they have the world’s largest collection of coronaviruses (genomic sequences and live viruses).
The knowledge, expertise, and resources are all readily available within the Hong Kong and mainland research laboratories (they collaborate extensively) to carry out and accomplish the work described below.
2.3. Final remarks
Many questions remain unanswered about the origin of SARS-CoV-2. Prominent virologists have
implicated in a Nature Medicine letter that laboratory escape, while not being entirely ruled out, was unlikely and that no sign of genetic manipulation is present in the SARS-CoV-2 genome4. However, here we show that genetic evidence within the spike gene of SARS-CoV-2 genome (restriction sites flanking the RBM; tandem rare codons used at the inserted furin-cleavage site) does exist and suggests that the SARS-CoV-2 genome should be a product of genetic manipulation. Furthermore, the proven concepts, well-established techniques, and knowledge and expertise are all in place for the convenient creation of this novel coronavirus in a short period of time. Motives aside, the following facts about SARS-CoV-2 are well-supported:
1. If it was a laboratory product, the most critical element in its creation, the backbone/template virus (ZC45/ZXC21), is owned by military research laboratories.
2. The genome sequence of SARS-CoV-2 has likely undergone genetic engineering, through which the virus has gained the ability to target humans with enhanced virulence and infectivity.
3. The characteristics and pathogenic effects of SARS-CoV-2 are unprecedented. The virus is highly transmissible, onset-hidden, multi-organ targeting, sequelae-unclear, lethal, and associated with
various symptoms and complications.
4. SARS-CoV-2 caused a world-wide pandemic, taking hundreds of thousands of lives and shutting down the global economy. It has a destructive power like no other. Judging from the evidence that we and others have gathered, we believe that finding the origin of
SARS-CoV-2 should involve an independent audit of the WIV P4 laboratories and the laboratories of their close collaborators. Such an investigation should have taken place long ago and should not be delayed any further.
We also note that in the publication of the chimeric virus SHC015-MA15 in 2015, the attribution of funding of Zhengli Shi by the NIAID was initially left out. It was reinstated in the publication in 2016 in a corrigendum, perhaps after the meeting in January 2016 to reinstate NIH funding for gain-of-function research on viruses. This is an unusual scientific behavior, which needs an explanation for.
What is not thoroughly described in this report is the various evidence indicating that several coronaviruses recently published (RaTG13, RmYN02, and several pangolin corona viruses are highly suspicious and likely fraudulent. These fabrications would serve no purpose other than to deceive the scientific community and the general public so that the true identity of SARS-CoV-2 is hidden. Although exclusion of details of such evidence does not alter the conclusion of the current report, we do believe that these details would provide additional support for our contention that SARS-CoV-2 is a laboratory-enhanced virus and a product of gain-of-function research. A follow-up report focusing on such additional evidence is now being prepared and will be submitted shortly.
Acknowledgements
We would like to thank Daoyu Zhang for sharing with us the findings of mutations in the E proteins in different sub-groups of β coronaviruses. We also thank all the anonymous scientists and other individuals, who have contributed in uncovering various facts associated with the origin of SARS-CoV-2.
References:
