SARS-CoV2 Variants and Vaccines mRNA Spikes Fibonacci Numerical UA/CG Metastructures

Comment: 1/ English language fully revised

2/ Abstract updated:
ABSTRACT.
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:
1/ SARS-CoV2 genome and spike evolution in one year 2020-2021. 2/ SARS-CoV2 Origins. 3/ Comparing 11 reference variants spikes. 4/ analysing 32 CAL.20C California variant  patients spikes. 5/ Toward a meta mRNA Fibonacci gene end message code. 6/ Analysing S501 UK, S484 South Africa and « 2 mutations » INDIA variants. 7/ Suggesting a possible variants spike mRNA  palindrome symmetry metastructure improving mRNA stability then infectiousness. 8/ Analysing Fibonacci Metastructures in the mRNA coding for the vaccines PFIZER and MODERNA. 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? 10/ 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.

Comment: One should also check, whether all the solutions and the materials employed for the production of the mRNA have been thoroughly autoclaved by using the cognate concentration of DEPC (diethypyrocarbonate), so that all the potential contaminating RNases are destroyed during the autoclaving process. Only with this kind of treatment are the liquids and materials devoid of RNases.

Comment: ........................................................................................................
Would it be possible to consider the following scientific article ?

The dawn of mRNA vaccines: The COVID-19 case

The dawn of mRNA vaccines: The COVID-19 case



The dawn of mRNA vaccines: The COVID-19 case

In less than one year since the outbreak of the COVID-19 pandemic, two mRNA-based vaccines, BNT162b2 and mRNA-12...

In the Table 1, the CVnCoV – CureVac is mentioned. The mRNA :

- has unmodified nucleotides

- is sequence-engineered

- has codon optimization

- is GC-enriched sequence

Would it be possible to perform the same kind of analyses with this mRNA «vaccine» ?

In the Figure 3, the S proteins produced as trimer constructs. This is requiring a full-length mRNA during translation.

What could happed if truncated mRNAs having their 5’-end intact are translated ? What kind of truncated would be generated, and what would be the consequences in therms of recognition of these epitopes ?

In the legend to Figure 4, we can read :

« Methods such as the introduction of modified nucleotides, the removal of dsRNA fragments, and sequence-engineering, can be utilized to minimize or control the type I IFN activity of mRNA. ».

This should be discussed.

In the Discussion section 6, we can read :

« More insights on the performance of the different LNP technologies, as well as detailed information on the mRNA sequence design (e.g., UTR inclusion, codon optimizations) might reveal (sometimes subtle) differences that can affect the potency and reactogenicity of mRNA vaccines. »

This should be discussed, too.