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COVID 19: The Spike and the Furin Cleavage

After months of insisting that COVID-19 originated in the Huanan Seafood Market in Wuhan, Gao Fu, director of the Chinese Centre for Disease Control and Prevention, stated that no viruses were detected in animal samples at the market.

According to May 31 report in the Daily Mail, Fu, the top epidemiologist in China said:

“At first, we assumed the seafood market might have the virus, but now the market is more like a victim.”

Fu also told the Daily Mail that “the novel coronavirus had existed long before.”1

This is consistent with the multiple studies showing that the COVID-19 virus was circulating in Wuhan before any person was infected at the seafood market.2,3

So where did it come from? Most governments and scientists are sticking with the official story put out by the Chinese Communist Party and most of the international mass media that SARS-CoV-2, the virus that causes COVID-19, has a natural origin, even though after months of searching, no natural host has been found. So far there is zero evidence for this, only data-free assumptions. As the well-respected scientist and critic of GMOs, Jonathan Latham points out:

“If the [Wuhan] lab has anything to hide, it is not only the Chinese Government that will be reluctant to see an impartial investigation proceed. Much of the work was funded by the U.S. taxpayers, channeled there by Peter Daszak and the EcoHealth Alliance. Virtually every credible international organisation that might in principle carry out such an investigation, the WHO, the US CDC, the FAO, the US NIH, including the Gates Foundation, is either an advisor to, or a partner of, the EcoHealth Alliance. If the Sars-CoV-2 outbreak originated from the bat coronavirus work at the WIV, then just about every major institution in the global public health community is implicated.”

The increasing body of evidence is showing that the most likely scenario is that SARS-CoV-2 was made in a lab and escaped.

Let’s look at the evidence.

The spike and the furin cleavage site

Several researchers have stated that SARS-CoV-2 is a combination of the bat coronavirus, RaTG13, supposedly collected in Yunnan (although Chinese lab scientists admit they have no sample in their possession of RaTG13, and many scientists doubt whether this bat coronavirus actually exists) and fully sequenced by the Wuhan Institute of Virology (WIV) in its laboratory in Wuhan in 2013, and spike protein from a coronavirus found in a Malayan Pangolin confiscated at the Chinese border by customs officials.4,5 The spike protein is unique, and the closest fit comes from the Malayan Pangolin.

It is highly unlikely that this recombination happened naturally, as it is improbable that these two viruses coexisted and merged in species that are separated by thousands of miles.6,7

The spike protein is found on the top of the spike on coronaviruses. It’s the part of the virus that attaches to cells to infect them. The spike protein of SARS-CoV-2 has a very special feature, a segment of four amino acids called a furin cleavage site. A furin cleavage site allows the virus to use furin in the human body as an enzyme to dissolve its coating so it can release its genetic material to infect cells. Furin cleavage sites tend to be more infectious than cleavage sites that use other enzymes.

The virus that caused the SARS epidemic, SARS-CoV, in 2002 - 2003 does not have a furin cleavage spike, so it was not as infectious as SARS-CoV-2.

There are several published papers showing that this four-amino acid sequence furin cleavage site is missing from the closest relatives of SARS-CoV-2 and has been inserted in precisely the best place in the spike protein to give it the ability to become highly infectious.8,9,10,11

It is highly improbable that this furin cleavage site has evolved naturally given that there is no sign of it evolving in any of SARS-CoV-2’s relatives in its clade. Viruses are sequenced, analyzed and grouped into clades. The viruses in the same clade are seen as having evolved (mutated) from the same ancestor.8

The furin cleavage site on SARS-CoV-2 is different from furin cleavage sites in other coronaviruses in that its combination of amino acids makes it more efficient at infecting people. This makeup of the SARS-CoV-2 cleavage site also allows many other enzymes, not just furin, to release its infectious genetic material. Consequently, several researchers are now calling it a multi-basic cleavage site. This unique amino acid combination means that SARS-CoV-2 is considerably more infectious than related coronaviruses. It also explains why the virus infects multiple organs and attacks the nervous systems.9,10

It is doubtful that this recombination of two viruses, plus the insertion of the most efficient multi-basic cleavage site in precisely the best place on the spike protein, happened naturally. Nothing close to this combination has been found in nature. It is more likely to have been constructed in a laboratory through Gain-of-Function research.

This type of complex combination would need many decades to evolve to the current structure to infect the first humans, and then evolve further to be highly infectious to humans. This was the case with SARS-CoV, where there is good evidence of very close relatives in nature and also evidence that its infectivity slowly evolved in people before it reached a level that caused the epidemic in 2002- 2003.

Research has shown that there is no evidence of evolving infectivity in humans in SARS-CoV-2. It was optimized to infect humans from day one. The researchers stated:

“Our observations suggest that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV. However, no precursors or branches of evolution stemming from a less human-adapted SARS-CoV-2-like virus have been detected.”12

A group of scientists used a computer model to test the way the SARS-CoV-2 spike protein bound with the receptors of the cells of many species. They discovered that the spike protein bound more strongly with human ACE2 receptor than any other species. They wrote:

“Notably, this approach surprisingly revealed that the binding energy between SARS-CoV-2 spike protein and ACE2 was highest for humans out of all species tested, suggesting that SARS-CoV-2 spike protein is uniquely evolved to bind and infect cells expressing human ACE2. This finding is particularly surprising as, typically, a virus would be expected to have highest affinity for the receptor in its original host species, e.g. bat, with a lower initial binding affinity for the receptor of any new host, e.g. humans. However, in this case, the affinity of SARS-CoV-2 is higher for humans than for the putative original host species, bats, or for any potential intermediary host species.”11

This is strong evidence that the virus was made in a laboratory rather than natural origins.

Lab-Made origins

The scientists who state that SARS-CoV-2 is not genetically engineered are basing their opinions on the lack of the insert signatures of genetic engineering. But this does not prove that it was not genetically engineered. Why? Because since 2001, Gain-of-Function virus researchers have been genetically modifying coronaviruses that have no evidence of GM insert signatures.

The first ever fully genetically engineered coronavirus was created by Ralph Baric and his team, and the information was published in 2002. In 2001, Baric’s team assembled a full-length mouse coronavirus and removed all the inserts that showed that it had been genetically engineered. They called this new method ‘No See’m Technology.’ This means that coronaviruses and other microorganisms can be genetically engineered without leaving any trace of the signatures of this engineering.13

In 2003, Baric and his team published another paper showing how they assembled a strain of SARS-CoV, the virus that caused the SARS epidemic in 2002-2003. This man-made virus was put together like a series of Lego blocks. Once the segments were joined, all the genetic engineering signatures were removed by using seamless joining of the segments they assembled.14

Baric and his team published a paper in 2008 on how they used genetic engineering to synthetically replicate a bat SARS-like coronavirus, and added the spike protein section of SARS-CoV that allows it to infect humans. This section is called the spike receptor-binding domain (RBD). The researchers stated:

“. . . we designed a consensus Bat-SCoV genome and replaced the Bat-SCoV Spike receptor-binding domain (RBD) with the SARS-CoV RBD (Bat-SRBD).”15

The researchers said they used the same seamless joining technique that they used in 2003 to assemble a human SARS virus (SARS-CoV). This means that the genetic engineering used to make this new bat virus with a spike protein that infects humans cannot be detected.15

Seamless joining has become so common now that it is routinely used in laboratories, and researchers can buy the tools to do it over the internet. As an example of a kit sold online:

“GeneArt® Seamless Cloning is a simple, two-step process, consisting of a tube-based assembly reaction followed by transformation into One Shot® Chemically Competent TOP10 E. coli. The kit uses the properties of a proprietary enzymatic mix to assemble DNA fragments with shared terminal end homology without leaving any extra sequences or scars behind (seamless).”16 

The concern here is that this technology is so widely available that anyone with a good knowledge of high school or university biochemistry can cook up a new disease organism in their kitchen and there would be no telltale signs that it was genetically modified.

This unregulated technology will result in more disasters.

Shi Zeng Li from WIV worked with Ralph Baric’s team in 2015 to genetically modify SARS-CoV in order to create a dangerous synthetic virus. The researchers took the genetic codes for part of the spike protein from a virus that Shi had isolated from bats found in Yunnan in 2011, and inserted them into SARS-CoV. Shi would have learned how to use Baric’s ‘No See’m Technology’ to make seamless joins that cannot be detected as GM signatures.17

In 2016, Shi and her team at the WIV, in conjunction with the New York-based EcoHealth Alliance, constructed a full-length clone of a bat coronavirus called SL-CoV WIV1. They assembled it in discrete segments. They genetically engineered the virus using the pGEM®-T Easy Vector Systems to join the segments. This system, also available on the internet, gives researchers several options for how to remove GM inserts that can be seen as signatures of a lab-made virus.18

The online pitch for pGEM®-T Easy Vector Systems states:

“Thus, several options exist to remove the desired insert DNA with a single restriction digestion.”19

This shows that researchers at the WIV have the ability to genetically engineer viruses and remove the signatures of the genetic engineering.

Shi Zhengli and other researchers at WIV and the EcoHealth Alliance, published a paper in 2017 on how they genetically modified the spike proteins of eight bat coronaviruses, by cutting and pasting genetic material from other coronaviruses, so that the viruses infected the human ACE2 receptor—the same receptor that SARS-CoV-2 infects to cause COVID-19. They used the pGEM®-T Easy Vector Systems to join the segments to genetically engineer these viruses. Very significantly, they showed how they can insert new spikes into viruses. The researchers state:

“Then any spike could be substituted into the genome of SARSr-CoV WIV1 through this strategy.”20

This shows that researchers at WIV have the ability to genetically modify multiple coronaviruses to insert new spikes, and these new viruses cannot be detected as genetically engineered.

The research clearly shows that Gain-of-Function researchers at WIV have the ability to assemble SARS-CoV-2 from bat coronaviruses, such as RaTG13 or similar, and the spike protein from the Malayan Pangolin, and insert the multi-basic cleavage site into the precise regions of the spike and leave no evidence of genetic engineering.

Lab escape

There is an enormous amount of evidence of disease organisms escaping from laboratories in China and other countries.21 Jonathan Latham and Allison Wilson, write about this evidence in Independent Science News. Latham and Wilson provide numerous examples, including how H1N1 flu escaped from a laboratory in 1977, causing a global pandemic, and how it broke out again in 2009, as Swine flu, causing around 3,000 deaths.22

Gain-of-Function research on coronaviruses was conducted in low-security Level-2 laboratories at the WIV, rather than the highest security Level-4 laboratory. The 2016 on how Shi and her colleagues constructed a full-length clone of a bat coronavirus states that the research was done at Level-2 laboratory. The 2017 on how they cut and pasted the spike proteins onto eight bat coronaviruses stated that they used the same methods as outlined in the 2016 paper, showing that this research was most likely done at the same Leve- 2 laboratory. Shi’s paper, published on May 14, 2020, on how they worked on the spike genes of multiple coronavirus referred to research conducted at the Level-2 laboratory.23

Given the information in the Washington Post about the inadequate level of biosecurity at the WIV, the escape of a coronavirus from the less secure Level-2 laboratory is a plausible scenario.24

SARS-CoV-2 was circulating in Wuhan before the first documented hospital case on December 1. According to the South China Post, the first case confirmed by the Chinese Government was on November 17, and there were more cases everyday afterwards. This has not been confirmed officially by the Chinese Government. However, given their continuous suppression of the facts, this comes as no surprise. The report in the South China Post shows that the first cases would have been in Wuhan in October.25

Another compelling piece of evidence was published in the journal Infection, Genetics and Evolution. The researchers behind that article traced back the rate of mutations in the various strain of SARS-CoV-2 to the Most Recent Common Ancestor (MRCA). The researchers wrote:

“. . . we observe an estimated tMRCA, which corresponds to the start of the COVID-19 epidemic, of 6 October 2019–11 December 2019.”26

The October 6 date is very interesting. According to an article published in NBC News, the cell phones around the Wuhan Institute of Virology went dark on October 7. The areas around the WIV, including the roads leading to it, went dark from October 14 -19, indicating that there were no people there or traffic on the roads. The lack of cell phone activity indicates that they emptied the Institute of people, and blocked the roads to stop traffic. This means that there may have been an accident on October 6 or 7, causing the need to evacuate the Institute and block of all access to and from it.27

While this cannot be proved at the moment, and it is highly unlikely that the WIV researchers and the Chinese government will ever tell the truth given the immense scale of the cover up, the weight of evidence clearly favors the scenario of an escape of a genetically modified virus as the most logical conclusion over the natural evolution theory for which there is zero evidence. There is nothing close enough to SARS-CoV-2 in nature to support the natural animal host theory, despite extensive searching by researchers.

The government officials and researchers involved in Gain-of-Function research are continuously denying it, however as the weeks go by, more cracks are appearing in their coverup and it is starting to fall apart. They know if the truth gets out about how Gain-of -Function research has caused this global pandemic, that has wrecked the lives of millions, the outcry and anger will be so great that this type of research will be banned.

André Leu is international director of Regeneration International. He is also author of several peer-reviewed papers and books. His latest book is “Poisoning our Children.”

References

1. https://www.dailymail.co.uk/news/article-8373007/Beijing-admits-coronavirus-DIDNT-start-Wuhans-market-DID-come-from.html?ITO=applenews

2. Chaolin Huang, Yeming Wang, Xingwang Li, Lili Ren, Jianping Zhao, Yi Hu, Li Zhang, Guohui Fan, Jiuyang Xu, Xiaoying Gu, Zhenshun Cheng, Ting Yu, Jiaan Xia, Yuan Wei, Wenjuan Wu, Xuelei Xie, Wen Yin, Hui Li, Min Liu, Yan Xiao, Hong Gao, Li Guo, Jungang Xie, Guangfa Wang, Rongmeng Jiang, Zhancheng Gao, Qi Jin, Jianwei Wang and Bin Cao, Clinical features of patients infected with 2019 novel  coronavirus in Wuhan, China, Lancet 2020; 395: 497–506, Published Online January 24, 2020 https://doi.org/10.1016/S0140-6736(20)30183-5

3. Botao Xiao and Lei Xiao, The possible origins of 2019-nCoV coronavirus, February 2020 https://chanworld.org/wp-content/uploads/wpforo/default_attachments/1581810860-447056518-Originsof2019-NCoV-XiaoB-Res.pdf

4. Peng Zhou, Xing-Lou Yang, Xian-Guang Wang, Ben Hu, Lei Zhang, Wei Zhang, Hao-Rui Si, Yan Zhu, Bei Li, Chao-Lin Huang, Hui-Dong Chen, Jing Chen, Yun Luo, Hua Guo, Ren-Di Jiang, Mei-Qin Liu Ying Chen, Xu-Rui Shen, Xi Wang, Xiao-Shuang Zheng, Kai Zhao, Quan-Jiao Chen, Fei Deng, Lin-Lin Liu, Bing Yan, Fa-Xian Zhan, Yan-Yi Wang, Geng-Fu Xiao & Zheng-Li Shi,  A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature, Vol579 12March2020

5. Kangpeng Xiao, Junqiong Zhai, Yaoyu Feng, Niu Zhou, Xu Zhang, Jie-Jian Zou, Na Li, Yaqiong Guo, Xiaobing Li, Xuejuan Shen, Zhipeng Zhang, Fanfan Shu, Wanyi Huang, Yu Li, Ziding Zhang, Rui-Ai Chen, Ya-Jiang Wu, Shi-Ming Peng, Mian Huang, Wei-Jun Xie, Qin-Hui Cai, Fang-Hui Hou, Yahong Liu, Wu Chen, Lihua Xiao and Yongyi Shen, Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins, bioRxiv preprint doi: https://doi.org/10.1101/2020.02.17.951335. this version posted February 20, 2020.

6. Xiaojun Li, Elena E. Giorgi, Manukumar Honnayakanahalli Marichannegowda, Brian Foley, Chuan Xiao, Xiang-Peng Kong, Yue Chen, S. Gnanakaran, Bette Korber, Feng Gao, Emergence of SARS-CoV-2 through recombination and strong purifying selection Science Advances doi:10.1126/sciadv.abb9153, May 2020

7. Matthew C. Wong, Sara J. Javornik Cregeen, Nadim J. Ajami, Joseph F. Petrosino, Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019 , bioRxiv preprint doi: https://doi.org/10.1101/2020.02.07.939207. This version posted February 13, 2020

8. B. Coutarda, C. Valleb, X. de Lamballeriea, B. Canardb, N.G. Seidahc, E. Decrolyb, The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin- T like cleavage site absent in CoV of the same clade, Antiviral Research 176 (2020) 104742

9. Jaimes, J.A., Millet, J.K., Whittaker, G.R., Proteolytic cleavage of the SARS- CoV-2 spike protein and the role of the novel S1/S2 site, ISCIENCE (2020), doi: https://doi.org/10.1016/j.isci.2020.101212.

10. Hoffmann M, Kleine-Weber H and Pöhlmann S 2020, A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells, Molecular Cell 78, 779–784 May 21, 2020  https://doi.org/10.1016/j.molcel.2020.04.022

11. Sakshi Piplani, Puneet Kumar Singh, David A. Winkler and Nikolai Petrovsky, In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus, arXiv:2005.06199 [q-bio.BM] 2020

12. Shing Hei Zhan, Benjamin E. Deverman, Yujia Alina Chan, SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence? bioRxiv preprint doi: https://doi.org/10.1101/2020.05.01.073262

13. Boyd Yount, Mark R. Denison, Susan R. Weiss, and Ralph S. Baric, Systematic Assembly of a Full Length Infectious cDNA of Mouse Hepatitis Virus Strain A59, JOURNAL OF VIROLOGY, Nov. 2002, p. 11065-11068 Vol. 76, No.21 DOI: 10.1128/JVI.76.21.11065-11078.2002

14. Boyd Yount, Kristopher M. Curtis, Elizabeth A. Fritz, Lisa E. Hensley, Peter B. Jahrling, Erik Prentice, Mark R. Denison, Thomas W. Geisbert and Ralph S. Baric, Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus, PNAS October 28, 2003, vol. 100, no. 22, 12995-13000

15. Michelle M. Becker, Rachel L. Graham, Eric F. Donaldson, Barry Rockx, Amy C. Sims, Timothy Sheahan, Raymond J. Pickles, Davide Corti, Robert E. Johnston, Ralph S. Baric and Mark R. Denison, Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice, PNAS December 16, 2008 105 (50) 19944-19949; https://doi.org/10.1073/pnas.0808116105

16. https://www.thermofisher.com/order/catalog/product/A13288#/A13288

17. Vineet D. Menachery, Boyd L. Yount Jr, Kari Debbink, Sudhakar Agnihothram, Lisa E. Gralinski, Jessica A. Plante, Rachel L. Graham, Trevor Scobey, Xing-Yi Ge, Eric F. Donaldson, Scott H. Randell, Antonio Lanzavecchia, Wayne A. Marasco, Zhengli-Li Shi & Ralph S. Baric, A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence, Nature Medicine Volume 21, Number 12, December 2015

18. Zeng L-P, Gao Y-T, Ge X-Y, Zhang Q, Peng C, Yang X-L, Tan B, Chen J, Chmura AA, Daszak P, Shi Z-L. 2016. Bat severe acute respiratory syndrome-like coronavirus WIV1 encodes an extra accessory protein, ORFX, involved in modulation of the host immune response. Journal of Virology 90:6573–6582. doi:10.1128/JVI.03079-15.

19. https://www.promega.com.au/products/pcr/pcr-cloning/pgem-t-easy-vector-systems/?catNum=A1360#overview

20. Hu B, Zeng L-P, Yang X-L, Ge X-Y, Zhang W, Li B, et al. (2017) Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog 13(11): e1006698. https://doi.org/10.1371/journal.ppat.1006698

21. Kaiser, J. (2007). BIOSAFETY BREACHES: Accidents Spur a Closer Look at Risks at Biodefense Labs. Science, 317(5846), 1852–1854. doi:10.1126/science.317.5846.1852

22. Jonathan Latham, PhD and Allison Wilson, PhD, The Case Is Building That COVID-19 Had a Lab Origin, Independent Science News, JUNE 2, 2020  https://www.independentsciencenews.org/health/the-case-is-building-that-covid-19-had-a-lab-origin/

23. Hua Guoa, Bing-Jie Hua, Xing-Lou Yanga, Lei-Ping Zenga, Bei Lia, Song-Ying Ouyangc, Zheng-Li Shi, Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes, bioRxiv preprint doi: https://doi.org/10.1101/2020.05.13.093658. this version posted May 14, 2020

24. https://www.washingtonpost.com/opinions/2020/04/14/state-department-cables-warned-safety-issues-wuhan-lab-studying-bat-coronaviruses/

25. https://www.scmp.com/news/china/society/article/3074991/coronavirus-chinas-first-confirmed-covid-19-case-traced-back

26. Lucyvan Dorpa, Mislav Acmana, Damien Richard, Liam P. Shaw, Charlotte E.Forda, Louise Ormonda, Christopher J.Owena, Juanita Pangae, Cedric C.S.Tana, Florencia A.T. Boshiere, Arturo Torres Ortiza, François Ballouxa, Emergence of genomic diversity and recurrent mutations in SARS-CoV-2,Infection, Genetics and Evolution Volume 83, 2020, 104351

27. https://www.nbcnews.com/politics/national-security/report-says-cellphone-data-suggests-october-shutdown-wuhan-lab-experts-n1202716

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