SARS-COV2 VARIANTS AND VACCINES MRNA SPIKES FIBONACCI NUMERICAL UA/CG METASTRUCTURES

In this paper, we suggest a biomathematical numerical method for analysing mRNA nucleotides sequences based on UA/CG Fibonacci numbers proportions.
This method is used to evaluate then compare the spike genes related to the main SARS-CoV2 VARIANTS currently circulating within the world population.
The 10 main results proposed to be reproduced by peers are:

SARS-CoV2 genome and spike evolution in one year 2020-2021.
SARS-CoV2 Origins.
Comparing 11 reference variants spikes.
Analysing 32 CAL.20C California variant patients’ spikes.
Toward a meta mRNA Fibonacci gene end message code.
Analysing S501 UK, S484 South Africa and « 2 mutations » INDIA variants.
Suggesting a possible variants spike mRNA palindrome symmetry metastructure improving mRNA stability then infectiousness.
Analysing Fibonacci Metastructures in the mRNA coding for the vaccines PFIZER and MODERNA.
Does the CG-rich modification of the synonymous codons of the spikes of the 2 mRNA vaccines affect the expression and quantity of SARS-CoV2 antibodies?
The exceptional case of the Brazilian variant P.1.

Particularly, we suggest the following conjecture at mRNA folding level:
CONJECTURE of SARS-CoV2 VARIANTS:
The growth of long Fibonacci structures in the shape of "podiums" for almost all of the variants studied (UK, California, South Africa, India, etc.) suggests the probable folding of the Spike mRNA in the form of a "hairpin", which can strengthen the cohesion and the lifespan of this mRNA.
Finally, we show that these kinds of Fibonacci matastructures disapear TOTALLY by analysing the published mRNA sequences of PFIZER and MODERNA vaccines. One fact is certain, the two mRNAs of the Moderna and Pfizer vaccines will result in a low functionality of the spike vaccine. This is because their designers by seeking greater stability, have doped to build CG rich sequences   which, as soon as they are inserted into the human host, will, paradoxically, seek to mutate, like SARS-CoV2 variants, towards CG ==> UA forms in order to improve their STABILITY and LIFETIME. We conclude using new biomathematics theoretical methods (Master code and numerical standing waves), and comparing the Spikes of the two vaccines Moderna and Pfizer, that there will be very probable differences in stability and shelf life of the two respective mRNAs vaccines. However, “State of the Art” analyzes will disclose that their two protein sequences are strictly identical. By modified their synonymous codons using different strategies, no one can guarantee that the quantity of antibodies generated will be identical in the two cases.
We wish to draw attention to the great ADAPTATION power - at the global scale of their genomes - of the most infectious VARIANTS, such as the BRAZIL 20J / 501Y.V3 variant (P.1). This is very worrying for the VACCINES <==> VARIANTS run: We demonstrate how the Brazilian variant P.1 which becomes uncontrollable in Brazil in April 2021 has a level of organization of long metastructures of 17,711 bases covering the genome which is 3.6 more important than that of the 2 reference genomes SARS-CoV2
 and worldwide D614G. We suggest that this high level of overall structure of this variant contributes to the stability of this genome and, might explain its greater contagiousness.
To complete this article, an ADDENDUM by Nobelprizewinner Luc Montagnier vas added at the end of this paper.


I-INTRODUCTION.
30 years ago, after pioneering in A.I (Perez, 1988(Perez, , 1991, we published in a paper entitled "chaos, dna, and neuro computers: the golden link" (Perez, 1991), a numerical method based on Fibonacci numbers to analyse dna sequences available at this time. In 2017 (Perez, 1997(Perez, , 2019, we revisited this method to démonstrate application of this method in mtDNA mutations involved on Human cancers. 58 years ago, (Montagnier L. § Kingsley Sanders F., 1963) Luc Montagnier had described the isolation of an infectious double helix RNA in cells infected with a picornavirus. It is perhaps likely that there is an analogous form in the coronavirus, specifically on VARIANTS mRNA spikes. This structure is very stable, resistant to RNase, and can therefore retain the genetic information of the virus for a long time. The palindromic structures detected here could constitute a "hairpin" double stranded RNA form.
II-METHODS and DATA SOURCES.

-Computing FIBONACCI metastructures:
Consider the sequence of Fibonacci numbers Example of the SPIKE from WUHAN reference genome, this mRNA SPIKE is 3822 bases UCAG in length. Recall WUHAN reference https://www.ncbi.nlm.nih.gov/nuccore/NC_045512 Severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome NCBI Reference Sequence: NC_045512.2 the longest Fibonacci structures would therefore measure 2584 bases. When looking for such structures, the first one found is in 1200 location: therefore, the bases located between 1201 and 3784 (1200 + 2584): These 2584 bases are broken down respectively into: 1597 bases UA et 987 bases CG Here are the first 20 basics that the reader can easily check: SPIKREF[1200+¼20] G U A A UU A G A G G U G A U G A A G U 0 1 1 1 1 1 1 0 1 0 0 1 0 1 1 0 1 1 0 1.../... The SPIKE analysis of this Wuhan-Hu-1 reference genome reports 63 metastructures of this type if we close the sequence on itself (as in mtDNA or bacteria) and 7 metastructures if we consider the mRNA sequence in its linear form, as will be the case throughout this study. Source (Da Silva Filipe et al, 2020), https://www.nature.com/articles/s41564-020-00838-z VARIANTS BRAZIL JAPAN (Naveca F et al, 2021) https://virological.org/t/phylogenetic-relationship-of-sars-cov-2-sequences-from-amazonas-withemerging-brazilian-variants-harboring-mutations-e484k-and-n501y-in-the-spike-protein/585

U AA U U A A U A U A A U 1597 bases UA G U A A UU A G A G G U G A U G A
Phylogenetic relationship of SARS-CoV-2 sequences from Amazonas with emerging Brazilian variants harboring mutations E484K and N501Y in the Spike protein second reference : (Gröhs Ferrareze P. A. , et al, 2021), E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil.https://www.biorxiv.org/content/10.1101/2021.01.27.426895v1 It is possible that S13I increases the efficiency of cleavage on the 12 amino-peptide terminal, which may increase the volume of S-protein on the host cell CAL.20C has three unique amino acid substitutions in its spike protein. The spike protein is the part of the virus that interacts and locks into proteins from the human host cell, essentially the key to open the host to the virus. Among these are S13I and W152C in the Nterminal domain, and L452R in the receptor-binding domain.
3.1-SARS-CoV2 genome and spike evolution in one year 2020-2021. At the level of the genomes, the very long Fibonacci metastructures (17711nt) increase a lot, which means a reinforcement of the overall mRNA structure of the genome. On the contrary, the overall metastructure of the spike seems to be reduced, although this variant has evolved at the level of amino acid mutations (mutations in CAL.20C california L452R, S13I, W152C).

3.2-SARS-CoV2 ORIGINS.
Fibonacci metastructures "shed a radically new light on" the relationships already recognized or suspected "between the 4 Sars-CoV2 Wuhan (1/2020), SARS-covZC45 (2017), SARS-covZXC21 (2015) and bat RATG13 genomes ( 2013). To this evidence of manipulation of CODONS synonymous with Spike of one or the other between SARS-CoV2 and beats RATG13, to the question "which of the 2 was manipulated?" (Perez, 2020), , (Castro-Chavez, 2020). We can assert that it is the SARS-Cov2 spike that has been manipulated to modify synonymous CODONS while retaining the functionality of the same amino acids. We believe that this manipulation will most certainly have attenuated the virulence and pathogenicity of SARS-) CoV2 opposite bat RATG13 * (blue regions of the 2 images of their Spikes). The following SARS-CoV2 "quadrille", bat RATG13, ZC45 and ZXC21 is remarkable for its enigmatic nature over the actual origins of SARS-CoV2. Indeed, when the first 2 are supposed to be of natural origin, we have the certainty and the proofs that the last 2 were read to the point -and published -by military laboratories. Fibonacci analysis of these 4 genomes and their Spike genes will reveal links, subfamilies and correlations 2 to 2 between these 4 key genomes in the history and genesis of the COVID-19 pandemic.
Genomes scale analysis :   Let us summarize the respective results of figures 5, 6 and 7: figure 5 (genomes) confirms the above dichotomy natural versus laboratory. indeed, a double vertical analogy clearly classifies these 4 genomes into 2 + 2 by the clear graphic correlation of their Fibonacci images.
On the contrary (figure 6 spikes), the comparative analysis of the 4 spikes clearly shows a horizontal dichotomy between SARS-CoV2 and ZC45 on the one hand and bat RATG13 and ZCX21 on the other hand. Does this mean that ZC45 would have served as a "model" for SARS-CoV2 while ZXC21 would have "inspired" bat RATG13, or rather the reverse if we take into account the respective dates: bat RATG13 (2013/2020) ZXC21 (2015 ) ZC45 (2017) SARS-CoV2 (2019/2020).
SARS-Cov2 is directly linked to RaTG13 as ZC45 is linked to ZXC21 and the reduction or even disappearance of the 2584 UACG metastructures in SARS-Cov2 and ZC45 shows that practically ZC45 is "made from" ZXC21 like SARS-Cov2 from RaTG13.
3.3-Comparing 11 reference variants spikes.     In this & 3, we try to answer the question: "Do the variants strengthen or reduce the level of Fibonacci metastructures of the Spikes vis-à-vis the original Wuhan and worldwife D614G strains?". We carry out 2 types of additional analyzes: on the one hand by considering the mRNA spike looped back on itself (ring like: figures 8 and 9), which is inaccurate here but nevertheless provides information which makes sense, which corresponds to the situation actual (figure 10 and table 2).
Globally, it appears a significant increase in Fibonacci structures for the variants, but these variants being only theoretical sequences, we will see in the following & that this increase in metastructure of the variant spikes is much more pronounced in the case of patients (see study of CAL.20C variant patients). This section analyzes the genomes and spikes of 32 patients with the California variant CAL.20C. Figure 11 and tables 4 to 6 summarize 2 major results: -the very great diversity of the results.

SPIKES
-the very clear trend of an increase in the number of Fibonacci structures compared to the reference genome D614G. But the new most remarkable is the one which will be the subject of the next & 5 ...
Data sources : GenBank.  Nota :For information, a first mutation is located in the HIV zone (S13I). 3 bases after kenya (1 in chart) and 8 bases before the second Hiv (2 in chart). See Perez §Montagnier 2020.
We analyzed here ( For the linear structures analysis of the spike (column 9), the integrity of the 32 cases increases these same metastructures 2584 AU / CG.
At the level of whole genomes, the 17711 UA / CG metastructures (column 11) increase in 30 out of 32 cases with respect to the reference genome D614G.
We can only conclude that the reference variants are only textbook cases, much less rich in synonymous mutations than the genomes of real patients. We conclude that a large number of synonymous mutations specific to each patient reinforce the overall structure of genomes and spikes, it suffices to observe the diversity of the results for each of the 32 patients.
Another remark, if all 32 patient cases have the L452R, for the 2 remaining mutations characterizing CAL.20C, there is a large diversity of individual cases for mutations S13I and W152C: someones have one or other or none between these mutations. There are also cases with deletions overlaping these S13I or W152C crucial mutations. Finally, we must conclude that the key of variants evolution and pathogenicity knowledge provides more from individual patients sequences full analysis that from theoretical reference variants description.   This point is at a level of fundamental research of mechanisms unknown to biology. Indeed, we demonstrate how, beyond and above the STOP codon which commands the protein manufacturing machinery to end the process, there would exist a sort of "end of gene message", which would be addressed to, on the scale of messenger RNA, this "code" would be digital in nature, carried by the ultimate UA / CG metastructure of Fibonacci. We observe that this message would be of Nature GIGOGNE, constituted like the Russian dolls of a nesting of proportions all ending on one of the 3 bases of the STOP codon. This discovery is validated in this article on 43 Spikes from UK, South Afrika, BRAZIL and CALIFORNIA variants. Of these Spikes, 32 were from real patients.
In each box of the penultimate column of table 3, there are 2 very close numbers: the first number 1597 is the optimal number of UA bases with a final resonance of 2584 UACG which would end in the immediate vicinity of the codon stop UAA of the Spike. The second number (ie. 1598) is the real number of UA bases contained among these last 2584 bases of the spike. Remember that 2584 bases cover 2/3 of the spike which has about 3800 bases. It is therefore a strong metastructure which would control the relative proportions of nucleotides in the spike.  Figure 13 histogram perfectly illustrating the "bell" concentration of cases around the 3 bases of the UAA stop codon of the spike. Table 7 and the histogram of FIG. 13 illustrate this remarkable phenomenon of "end-ofgene meta-structure" generalized to the 32 spike strains of CAL.20C patients plus 11 spikes of reference variants, for a total of 43 cases. The histogram perfectly illustrates the "bell" concentration of cases around the 3 bases of the UAA stop codon of the spike.

Mutation Information
S:N501 has appeared multiple times independently: each can be associated with different accompanying mutations Amino-acid changes are S:N501Y (nucleotide mutation A23063T), S:N501T (nucleotide mutation A23064C), and S:N501S (nucleotide mutation A23064G) For this South African variant (figure 15), we see above all a strong increase in metastructures 1597 UACG (orange in figure 15).
On the other hand, the "podium" shape, already observed for the English variant, becomes very clear here. This enigmatic form will be the subject of the next and last paragraph & 7 ...

Full variant
In BASIC VARIANT, we modify spike D614G only with these 2 mutations:E484Q and L452R.
In 3.7-Suggesting a possible variants spike mRNA palindrome symmetry metastructure improving mRNA stability then infectuosity.
Here, we have gathered several pieces of evidence showing that, as they evolve, the variants would constitute and reinforce a kind of Palindrome-type symmetry based on "Russian doll" interlocking of their MRNA, which could lead to a double strand. of the "hairpin" type, thus reinforcing the stability and the lifespan of the Spike MRNA, thus certainly the increasing contagiousness of the variant virus. Clearly more pronounced "PODIUM-like" structures appear in these UK, South Afrika, India, California (figures 14 to 17) variants than in the strain D614G Spike.
The structures in orange 1597UACG form a curious "PODIUM" ... It does appear C <==> G relations on the hypothetical double strand of mRNA.
Paticularly, we suggest the following conjecture at mRNA folding level (Mengwen et al, 2006): The growth of long Fibonacci structures in the shape of "podiums" for almost all of the variants studied (UK, California, South Afrika, India, etc.) suggests the probable folding of the Spike mRNA in the form of a "hairpin", which can strengthen the cohesion and the lifespan of this mRNA. Then we analysed using the same method the hypothetic metastructure of this mRNA vaccine...

Recall the 100 first bases of SARS-CoV2 Spike : ATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCA GAACTCAATTACCCCCTGCATACACTAATTCTTTCACAC
It is interesting comparing this region with the same areas in both vaccines ( bold ).
What should we conclude about this total absence of Fibonacci metastructures in the mRNAs of these 2 vaccines? This means that, although functional, these mRNAs will have a short lifespan and their overall physical structure will be very weak. These mRNAs will be able to split rather quickly into separate fragments which will risk combining with other mRNAs present in their environment.  We will now explain the technological reasons which, in the design of these 2 vaccines, led to such differences between the Fibonacci structures of real sarscov2, their variants and these 2 mRNA vaccines. A necessary but not sufficient condition for the possible emergence of Fibonacci UA / CG metastructures is that the ratio between the total number of UA and CG bases of the analyzed sequence is> 1 and, ideally, close to the optimum Phi = 1.618, the "Golden ratio". Let us calculate these ratios for certain sarscov2 genomes and spikes various variants, then for the 2 mRNAs of the Moderna and Pfizer vaccines.

1.00481884
Faced with such a distortion between the real and "humanized" SARS-CoV2 strains and its variants on the one hand, and the mRNAs of the 2 vaccines on the other hand, we will now try to answer 2 essential questions: 1 / Is there a mutation "strategy" governing the adaptation of the virus and its variants to its host? This strategy, if it exists, will ALSO constitute a strong mutation constraint for the 2 mRNAs of the Moderna and Pfizer vaccines? Table 10 below will answer this key question.
2 / For what technological reasons did the designers of the 2 mRNA vaccines decide to "dope" the sequences constituting their vaccines in CG bases?
Does this predominance of AU / CG ratios located around Phi = 1.618 extend to other SARS-CoV2 genes? In
Recall SARS-CoV2 Wuhan references https://www.ncbi.nlm.nih.gov/nuccore/NC_045512  « For what technological reasons did the designers of the 2 mRNA vaccines decide to "dope" the sequences constituting their vaccines in CG bases? » In (Jackson et al, 2020), we could read : «Last, codon optimization and modification of nucleotides have contributed to translation efficiency. For example, optimization of guanine and cytosine (GC) content can have a significant impact (Kudla et al, 2016) and has been well established with DNA vaccines ». (Kudla et al, 2016) detailed this « CG rich manufacturing technology » : « Mammalian genes are highly heterogeneous with respect to their nucleotide composition, but the functional consequences of this heterogeneity are not clear. In the previous studies, weak positive or negative correlations have been found between the silent-site guanine and cytosine (GC) content and expression of mammalian genes. However, previous studies disregarded differences in the genomic context of genes, which could potentially obscure any correlation between GC content and expression. In the present work, we directly … » Of full list of 18 nucleotide mutations, 15 are mutations to T (possibly related to APOBEClike editing within host, see (Simmonds, 2020). This variant is found in at least 10 countries across Europe.

S:D80Y
S:D80Y is the opposite end of the loop 'tucked in' by the 69/70 deletion (hypothetical association). See MutationS:H69for more detail on the impact of 69/70 deletion.
This strain is present everywhere in Europe. Quite rightly, Professor Luc Montagnier asks me: "I put my question again in another form: all the variants that you have studied have in the sequence of their Spyke proteins a Fibonacci YES series? Why? because it is a rule of harmonization of Nature followed by the variants during their passage through their successive hosts. The m-RNA sequences of vaccines were chosen by technologists ignoring these laws, which only had the aim of increasing the stability of their messages." This is why I researched and found what technological reasons led them to make mRNA CG rich.
But another more speculative question then arises: Between these 2 disjoint universes that are mRNA and proteins, would having a HYPER STRUCTURED mRNA be able to transmit "a certain dynamic energy during the passage into amino acids" to the future protein, which would make it more stable? , more functional? If so, our Fibonacci are used for that.One fact is certain, the 2 mRNAs of the Moderna and Pfizer vaccines will result in a low functionality of the spike vaccine because by doping these sequences in CG rich, their designers, in search of greater STABILITY of these RNAs will have built, according to us , sequences which, as soon as they are inserted into the human host, will seek to mutate, like SARS-CoV2 variants, towards CG ==> UA forms in order to improve, paradoxically, their STABILITY and probably also their LIFETIME.
3.9 -Does the CG-rich modification of the synonymous codons of the spikes of the 2 mRNA vaccines affect the expression and quantity of SARS-CoV2 antibodies?
Analyzing Master Code fractal structure and stationary waveforms differences between Moderna and Phizer Spikes mRNA.
In (Perez, 2015 andPerez, 2018), we present a unifying theoretical method, from the atomic masses of their bioatoms C O N H S P, the 3 biological universes of RNA, DNA and proteins. We published various articles involving applications based on this basic research (Perez, 2017b, Perez, 2017c.
The Master Code of the sequence can be applied indistinctly to all DNA or RNA sequences irrespective of the fact that they are coding proteins or not, and to all protein sequences.
To every nucleotide triplet (codon), or amino acid (AA), can be associated a cypher comprised between -3 and +7. These cyphers were established in relation with the atomic masses of the chemical elements C,N,O,H,S,P constituting the nitrogen bases (purines and pyrimidines) and the amino acids. They allow a simple numerical translation of the 64 codons and 20 amino acids. Exposing here the concepts leading to this code goes beyond the scope of this article and we refer the budding mathematicians to the article (Perez, 2018) "Six Fractal Codes of Biological Life: perspectives in Exobiology and Artificial Intelligence Biomimetism Decisions Making, 2018". One could oppose the criticism that this representation reduces too drastically the physico-chemical reality of the translated sequences. However, it allows their underlying geometrical reality to be measured. This mathematical conversion has the advantage to reduce the complexity of the problem. We can cite here the great mathematician and physicist Von Neumann who used to say with humor "There's no sense in being precise when you don't even know what you're talking about".
Although the amino acid sequences of the spikes of the 2 mRNA vaccines are identical, it is interesting to analyze with these biomathematic methods their nucleotide sequences which are very different. Indeed (& 3.8), we have seen that these 2 sequences were doped with CG rich nucleotides at the level of the synonymous codons coding for the same amino acid, therefore without affecting the sequence of the spike protein.
In Figure 23 below, we see that, while the 2 Moderna and Phizer protein sequences (blue proteomics curves) are identical, their respective Genomics curves (red curves) are very different. We observe in particular a completely chaotic fractal roughness in the case of Phizer spike. In fact, in the case of the 2 spikes of these vaccines, a large number of synonymous codons were modified in order to dope these sequences in CG bases without altering the amino acid sequence. We believe that this exceptional fractal roughness could affect the stability and the lifespan of the RNA, whereas the corn sought by the designers of Pfizer-Biontech was, precisely, to increase the stability of these RNAs. One advantage will be that these RNAs will be quickly destroyed (around ten days). On the other hand, the fragility of these RNAs could lead to "breaks" of the RNA strand, with the risk of erratic combinations (HERV retrovirus for example, naturally present in the cell). Computing Standing waves : In (Perez,2018), we describe this biomathematical method associating with any Genomics sequence periodic waves (numerical where period is a number of nucleotides). The Genomics master code is generalized to meta-codons that no longer have 3 nucleotides as a codon, but 4, 5, … 100 nucleotides. Then we analyze the textures by the undulatory code. It then appears dissonances and resonances that will reveal periods of discrete waves, resonances, and standing waves. This method provides a global analysis of the roughness or fractal texture of the DNA sequences at the whole sequence scale. To do this, we generalize the method of numerical analysis of the "Master Code". Thus, we restructure the sequence into different generic sequences based on "meta codons", no longer triplets of 3 nucleotides, but values ranging from 1 to 100 nucleotides. This method of analysis will then reveal, in most cases, discrete waves or interferences, most often dissonances resulting from Genomics Master code texture analysis. However, sometimes there will emerge kinds of resonances where all scales of analysis appear to be in symbiosis.
The following Figure 24 shows this kind of waveforms in the 3 cases of Spike sequences providing from SARS-CoV2 Wuhan reference, Moderna vaccine and Phizer vaccine. Figure 24 below illustrates and confirms, as before, standing waves of 8 nucleotides quite similar for SARS-CoV2 and Moderna spikes. On the contrary, the Spike Phizer is characterized by a different frequency: period of 7 nucleotides. From this comparison of the Spikes of the 2 vaccines Moderna and Phizer, we conclude a very probable difference in stability and shelf life of the 2 respective mRNAs of these 2 vaccines. However, the "State of the Art" will tell you that their 2 protein sequences are strictly identical. However, by having modified their synonymous codons using different strategies, no one can guarantee that the quantity of antibodies generated will be identical in the 2 cases. No one can affirm that this difference in the 2 mRNAs will not have contributed to the dynamic formation of the spike protein. This is all the more complex since these mRNAs contain certain modified U / T bases. Professor Roland Baker (Molecular Genetics, U.C. Berkeley) said me " T is for thymine used in DNA. U is for uracil used instead of T for mRNA. The mRNA vaccines made by Moderna and Pfizer use neither. Instead they use 1methyl-3'-pseudouridylyl which is either shows a m1Ψ or simply Ψ. 1-methyl-3'pseudouridylyl is used to increase the half-life of the mRNA. Otherwise it degrades too quickly. " One might wonder why such a period of 8 nucleotides is important? We observe that the spikes of SARS-CoV2 (and all its variants), as well as the Moderna spike, retain this period 8, unlike the Phizer spike. 8 is a Fibonacci number, and Figure 25 below illustrates how these Fibonacci periods (8 13 21 34 55 89 ...) are conserved at the scale of whole genomes SARS-CoV2 wuhan, but also in this variant CAL 21C collected from a Californian patient (Table3, CA51). It even appears that these Fibonacci standing wave periods at the scale of the entire genome would be "reinforced" in the case of the Californian variant ( Figure 25).
Although these 2 genomes are significantly different (29903nt for SARS-CoV2 and 29754nt for CA51). CA51 contains one deletion encompassing S13I and another deletion encompassing W152C (see Table3), 2 of the 3 characteristic mutations of the California variant CAL.20C. However, despite this high level of deletions of the CAL.20C genome, the level of Fibonacci standing waves is preserved and even here reinforced. At the same time, the number of Fibonacci UA / CG metastructures (Table3) is also reinforced with respect to the reference genome.

IV-CONCLUSIONS.
First, this study of Spikes by Fibonacci metastructures highlights 4 first conclusions: -It presents a clarification by the image of links already suspected by multiple researchers between the spikes of bat RATG13, ZXC21, ZC45 and SARS-CoV2.
-As we had predicted and already verified (WA state USA) in , some variants deleted as a priority our predicted « EIE » HIV-like fragments from the dense HIV region at the start of the spike. This is the case with the English variant but also with several patients of the California variant CAL.20C.
-Overall, the reference spikes of all the variants studied here have a reinforcement of the most significant Fibonacci structures (2584 bases). But this phenomenon is amplified and confirmed when we analyze the spikes of patients (32 CAL.20C patients).
-We note the total absence of Fibonacci metastructures in the mRNAs of both mRNA vaccines PFIZER and MODERNA. This means that, although functional, these mRNAs will have a short lifespan and their overall physical structure will be very weak. These mRNAs will be able to split rather quickly into separate fragments which will risk combining with other mRNAs present in their environment.
We will also conclude the tendency of the variant spikes to strengthen their overall structure, which may be correlated with their greater cohesion and lifespan of their mRNA spike, and probably the greater infectivity and pathogenicity of the variants.
Of the 7 clusters of results presented here, 3 will deserve to be revisited, reproduced and extended more deeply: 1 / point -II-Fibonacci metastructures "shed a radically new light on" the relationships already recognized or suspected "between the 4 Sars-CoV2 Wuhan (1/2020), SARS-covZC44 (2017), SARS-covPZXC2P1 (2015) and bat RATG13 genomes ( 2013). To this evidence of manipulation of CODONS synonymous with Spike of one or the other between SARS-CoV2 and beats RATG13, to the question "which of the 2 was manipulated?". We can assert that it is the SARS-Cov2 spike that has been manipulated to modify synonymous CODONS while retaining the functionality of the same amino acids. We believe that this manipulation will most certainly have attenuated the virulence and pathogenicity of SARS-) CoV2 opposite bat RATG13 * (blue regions of the 2 images of their Spikes). Moreover, if at the level of the 4 respective genomes, the strong neighborhoods between SARS-CoV2 and bat RATG13 on the one hand, and ZC45 and ZXC21 on the other hand are confirmed by these Fibonacci metastructures (vertical analogies in the image), a less expected bi-duality is highlighted at the level of their 4 respective spikes: on the one hand, this obvious neighborhood between ZXC21 and bat RATG13, and, on the other hand, although less obvious, this other neighborhood between ZC45 and SARS -CoV2 (horizontal analogies in the image).
2 / the point -V-This point is at a level of fundamental research of mechanisms unknown to biology. Indeed, we demonstrate how, beyond and above the STOP codon which commands the protein manufacturing machinery to end the process, there would exist a sort of "end of gene message", which would be addressed to, on the scale of messenger RNA, this "code" would be digital in nature, carried by the ultimate UA / CG metastructure of Fibonacci. We observe that this message would be of Nature GIGOGNE, constituted like the Russian dolls of a nesting of proportions all ending on one of the 3 bases of the STOP codon. This discovery is validated in this article on 43 Spikes from UK, South Afrika, BRAZIL and CALIFORNIA variants. Of these Spikes, 32 were from real patients.

/ point -VII-
Here, we have gathered several pieces of evidence showing that, as they evolve, the variants would constitute and reinforce a kind of Palindrome-type symmetry based on "Russian doll" interlocking of their MRNA, which could lead to a double strand. of the "hairpin" type, thus reinforcing the stability and the lifespan of the Spike MRNA, thus certainly the increasing contagiousness of the variant virus.
In (Demongeot § Henrion-Caude, 2020), Alexandra Henrion-Caude and Jacques Demongeot proposed in 2020 a possible universel starting RNA 22 nucleotides sequence which could be a candidate bootstrap at origins of Life in a RNA primitive world.
Professor Luc Montagnier observes that these authors attribute an essential role in the origin of life to a circular RNA of 22 nucleotides. This is the length of our "EIE" (Exogenous Insertion Elements) in SARS-CoV2 genome published in https://zenodo.org/record/3975578 Particularly, this hyper constrainst circular 22nt sequence codes for the 20 amino acids + codon stop + only one redondant amino acid (MET). We found this archaic mRNA sequence using BLASTn long (14nt) contiguous sequences in HIV mRNA genomes... and also in SARS-CoV2 Wuhan reference mRNA genome ! But consider the circular character of this primitive RNA 22 nucleotides long UCAG. So, here is our original result on its multiple and SYSTEMATIC Fibonacci proportions as soon as it is a CIRCULAR RNA sequence ... 5' AUGGUACUGCCAUUCAAGAUGA 3' AUGGUACUGCCAUUCAAGAU G ==> A 13AU 8CG AUGGUACUGCCAUUCAA G ==> AUGA 13AU 8CG AUGGUACUGCCAUU C ==> AAGAUGA 13AU 8CG AUGGUACUGC C ==> AUUCAAGAUGA 13AU 8CG AUGGUACUG C ==> CAUUCAAGAUGA 13AU 8CG AUGGUACU G ==> CCAUUCAAGAUGA 13AU 8CG AUGGUA C ==> UGCCAUUCAAGAUGA 13AU 8CG AUG G ==> UACUGCCAUUCAAGAUGA 13AU 8CG AU G ==> GUACUGCCAUUCAAGAUGA 13AU 8CG Seen from the point of view of the autopoiesis Francisco Varela theory (ref Varela), autonomy of Indoor vs. Outdoor systems) these results could be interpreted as the rest of the loop of 21 UACG (outdoor) "seen" from a base C or G (indoor). So the perceived signal is a kind of Fibonacci resonance ... By virtue of Francisco Varela's theory of autopoiesis (Varela § Maturana, 1980) that we applied to Artificial Intelligence in the 1980s by creating the "fractal chaos" artificial neural network (Perez 1988). Thus, the Fibonacci numbers, therefore the optimal proportion of the golden ratio would perhaps have already been present from the first moments of life on earth, a life for which they would have served as a "matrix" … "If I followed correctly, the circular RNA sequence obeys the Fibonacci rule. If we extrapolate, we can think that Life was formed (or was created, according to our religion) from this RNA according to a mathematical principle? "LM?
Actually, the RNA sequence proposed by the article by Alexandra Henrion-Caude, which seems to "spring" from nowhere can only intrigue the reader. Indeed, what is certain with this sequence is that God, or panspermia, or self-organization are indeed Mathematicians ... Indeed : They already know how to count 4 + 5 + 6 + 7 = 22. I meant 4C, 5G, 6U, 7A Let C + G = 9 U + A = 13 We are already very close to the 13/8 = Phi ratio, the same one that we can verify in all SARSCOV2 genomes. But also, pyrimidine purines: 4C+6U=10UC 5G+7A=12AG 10=2x5 12=2x6 5 and 6 these 2 key numbers associated with the harmonious but unstable shape of the Pentagon (5) and the harmonious but stable form of the Hexagon (6).
It is no coincidence that Nature (flowers) or religions -also -have invented stars with 5 or 6 branches ....
And the structure of RNA and DNA are built around Pentagons and Hexagons ...And "Pollack's Water Fourth state" structure of WATER ( https://www.pollacklab.org/ ), also built around the hexagon ... So EVERYTHING seems to be potentially written in these 22 nucleotides ...
We also note 2x6 = 12 bases in primers of palindromes or mirror series: AUGGUA mirror and UCAAGA quasi palindrome.
Finally, we will note cs 5 triplets of consecutive nucleotides: GAA UGG GCC AUU CAA Symetries purines pyrimidines on 4 of the 5 TRIPLETS UGG CAA

GCC AUU
Finally, we must recall this open question : CONJECTURE of SARS-CoV2 VARIANTS: The growth of long Fibonacci structures in the shape of "podiums" for almost all of the variants studied (UK, California, South Afrika, India, etc.) suggests the probable folding of the Spike mRNA in the form of a "hairpin", which can strengthen the cohesion and the lifespan of this mRNA.

Three final conclusions :
One fact is certain, the 2 mRNAs of the Moderna and Pfizer vaccines will result in a low functionality of the spike vaccine because by doping these sequences in CG rich, their designers, in search of greater STABILITY of these RNAs will have built, according to us, sequences which, as soon as they are inserted into the human host, will seek to mutate, like SARS-CoV2 variants, towards CG ==> UA forms in order to improve, paradoxically, their STABILITY and probably also their LIFETIME... Secondly, using new biomathematics theoretical methods (Master code and numerical standing waves), and comparing the Spikes of the 2 vaccines Moderna and Phizer, we conclude a very probable difference in stability and shelf life of the 2 respective mRNAs of these 2 vaccines. However, the "State of the Art" will tell you that their 2 protein sequences are strictly identical. However, by having modified their synonymous codons using different strategies, no one can guarantee that the quantity of antibodies generated and sensitivity to variants will be identical in the 2 cases (Kustin et al, 2021).
Despite the immense progress of Biology, the RNA universe remains today still full of unexplained mysteries. However, it is said, as we will see, that it would have constituted the first crucible of life. This is why we will have to exercise the greatest caution, on the one hand in the face of an mRNA virus such as SARS-CoV2, but even more in the face of the unpredictable evolution of new vaccines, themselves based on RNA. V-ACKNOWLEDGEMENTS.