Ranpirnase degrades Covid vaccines mRNA and prevents the formation of the proteotoxic effect related to wrong codon usage

Given codon optimization errors involving a methylated form of psudouridine and various risky substitutions, only an RNAse agent can degrade mRNA

There is evidence that various alterations in the genetic sequence of the mRNA of the Covid Pfizer vaccine named BNT162b2, compared with the genetic code of the natural viral counterpart of Sars-CoV-2, cause a high probability by the organism's ribosomal mechanism to incur serious errors in reading, translating and executing the instructions contained in the mRNA itself, as demonstrated in the article by Dr. Kira Smith published Feb. 5, 2021 on Longdom's International Journal of Antivirals and Antiretrovirals, later removed and available, however, on ResearchGate at this link:

https://www.researchgate.net/publication/354153084_Mini_Review_Correspondence_to_BNT162b2_Vaccine_Possible_Codons_Misreading_Errors_in_Protein_Synthesis_and_Alternative_Splicing's_Anomalies

This was only the first research paper to highlight several factors capable of causing problems in the recipient organism of the Covid vaccine, but a huge number have been published over time, until the recent noteworthy study conducted by researchers at the University of Cambridge, published in December 2023 on Nature, which demonstrates the occurrence of ribosomal frameshifting +1 phenomenon in vivo; this indicates a general lack of overall sequence stability and, as a result, production of elements of unknown toxicity and functions, other than the designated S Spike protein:

https://www.nature.com/articles/s41586-023-06800-3

Although the researchers claimed to have found no serious consequences in humans, despite to referring to a study limited to 21 individuals, as well as stating this only for the purpose of being able to publish the research work, even receiving international praise from professors at other leading universities and thanks from Pfizer, which confirmed the study's usefulness to improve this aspect in the future, it is unknown whether it’s really harmless, especially upon the occurrence of the above abnormal phenomenon in conjunction with other risk factors for global mRNA stability.

It’s clear that +1 ribosomal frameshifting together with the presence of rigid secondary structures in the mRNA leads to allow ribosomes to easily move back and forth can cause frameshifting with high frequency, which result in strong ribosome pausing or stalling in translation systems. In addition, ribosomal stalling can cause premature translation termination, thus reducing translation efficiency, that usually lead to early termination and truncated protein products.

In addition, P-body transcriptome analyses suggest that GC content can influence mRNA storage in P-bodies and mRNA decay in human cells. Although increased expression is the desired outcome of codon optimization, it’s necessary to control over-expression to avoid the confounding influence of stress on the quality control machinery of the cell. There are many studies suggesting that ribosomal pauses schedule co-translational folding of protein domains, and determine the final protein conformation.

Of note, increased protein expression, mediated by codon pair optimization, was reported to occur in the absence of increased mRNA levels, and there is evidence suggesting that codon pair usage changes may be involved in human diseases. Nevertheless, codon pair frequencies did not correlate with the ribosome profiling data.

The degeneracy of genetic codons, predominantly due to flexibility in the identity of the third nucleotide—in what is known as the wobble position—allows 18 of the 20 standard amino acids to be encoded by two to six synonymous codons.

Because synonymous codon mutations do not change protein sequences, synonymous codons were previously considered to be redundant, and their mutations were regarded as silent mutations. Many human diseases are associated with silent SNPs, but whether codon usage changes contribute to human diseases caused by these SNPs is still not clear, since it was shown that the supposed ’silent’ mutations can have an impact on human health through various mechanisms. One of these mechanisms is protein misfolding, which occurs by means of an alteration of the ribosome-mediated translational attenuation program.

The main idea underlying the protein-misfolding based mechanism, is that codon usage can modulate ribosome traffic and, consequently, co-translational folding, by means of associating frequent codons with fast elongation rates and rare codons with slow elongation rates. However, the exact mechanism connecting proteostasis with codon usage remains unclear.

In a research article are reviewed 22 genetic diseases or traits associated with synonymous mutations. It is known that the genetic condition for multidrug resistance is a consequence of the protein-misfolding based mechanism, whereas three other of these 22 diseases (Crohn’s disease, cystic fibrosis and TMD) are the result of different mechanisms, but to common root.

In addition, tRNA quality is also related to tRNA modifications, therefore, it will be worthwhile to examine the effects of tRNA modifications on mRNA stability, since tRNAs are master gene regulators and highlight the need to fully understand how tRNA expression and processing are regulated in different cells and various conditions, including human diseases.

Given this background, it has been said it may prove useful to set out to find an agent that can degrade mRNA before it does irreparable damage.

At the end of this intricate research work, it has been established and demonstrated that the enzyme Ranpirnase, from the large class of protein named ribonucleases (RNAse), and it’s able to perform the task perfectly, without causing adverse side effects and without likelihood of lead to the onset of pathological events in any individual receiving its administration, since it is an extracted from the Northern leopard frog, Rana pipiens.

As a ribonuclease, Ranpirnase degrades breaking down RNA molecules in cells, and resulting in an inhibition of protein synthesis; since cells with higher levels of tRNA than normal cells, such as cancer cells, are more susceptible to the effects of Ranpirnase, its anticancer properties have been studied, with a view to future applications in this field. However, it is observable the effectiveness of the application aimed at degrading exogenous mRNA, preventing the formation of harmful elements, such as prions and amyloids.

The enzyme Ranpirnase acts on errors in the structure of an mRNA, degrading it. The enzyme recognises specific features or defects in the mRNA structure, such as the presence of loops or mismatched regions, and catalyses their degradation. This degradation process is important for maintaining the integrity and quality of cellular mRNA by eliminating defective or poorly structured mRNA. The enzyme Ranpirnase plays a key role in mRNA quality control, contributing to the selective removal of mRNAs with structural errors, which could lead to malfunctioning or production of non-functional proteins.

The enzyme Ranpirnase may play an indirect role in preventing the formation of amyloids and prions. Amyloids are insoluble protein aggregates that can be formed by misfolded proteins or proteins with structure errors. Prions, on the other hand, are abnormal proteins that can cause neurodegenerative diseases such as Creutzfeldt-Jakob disease.

Since the enzyme Ranpirnase is involved in the degradation of defective or poorly structured mRNAs, it can help remove mRNAs that code for proteins with structure errors or that can cause amyloid or prion formation. By removing these defective mRNAs, the Ranpirnase enzyme can indirectly reduce the production of abnormal proteins and thus prevent the formation of amyloids and prions.

However, it is important to emphasise that the formation of amyloids and prions is a complex process influenced by many factors. The enzyme Ranpirnase may play a key role in preventing such formations, but it is not the only factor involved.

The indicated dosage ranges from 65 mcu to 650 mcu, based on individual and pathological factors evidenced. More specifically, in humans the effective dosage ranges from 30 mcg/kg to 120 mcg/kg, administered via intravenous route, once a day, for 3-5 consecutive days, with a withdrawal period of 9-16 days. This cicle should be repeated at least a second time in those manifesting initial non-critical symptoms, while those showing a severe clinical conditions should repeat treatment a 3rd time, followed by an observation period.

Ribonuclease mechanism performed by Ranpirnase