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Yesterday, December 27, 2020, Italy began administering the first doses of the vaccine. BNT162b2 developed by BioNTech / Pfizer. While waiting for a truly effective therapy against SARS-CoV-2 that currently does not exist, vaccination is the only weapon that humanity has at its disposal to combat a virus that few, just a year ago, believed capable of creating so many problems for the whole world.
The virus, now known, belongs to the domain of Riboviria and is part of the family of Coronaviridae; SARS-CoV-2 is a pathogen endowed with positive single-stranded RNA wrapped in an external layer (capsid), in turn covered by a very thin pericapseid on which peplomers, simple glycoproteins (the famous “spike” proteins) are found. ) responsible for the degree of pathogenicity of the virus in question. Wanting to exemplify everything, the virus could be compared to a soccer ball with an air chamber, on the outer surface of which there are many “spikes”.
The purpose of this article is not to enter the maze of microbiology or virology, but to better understand everything it is good to make some initial considerations.
the DNA it is the genetic code present in every cell of our body: it is a kind of hard disk, a physical memory in all aspects that contains all the information that the body needs to function. Inside the DNA double helix there are nucleotides whose sequence of nitrogenous bases is responsible for the synthesis of the proteins necessary for the growth and survival of a living being; If in computing there is a binary code (composed of sequences of 0 and 1), in the cells a sequence of nitrogenous bases is sufficient, identified by the letters A me GRAM (Adenina e Guanina, dette “purine”), C me T (Cytosine and Timina, dette “pyrimidine”).
L ‘RNA it is, on the other hand, a genetic code derived from DNA, the true “link” between the information present in the DNA itself and what will be the end result of the various metabolic processes of the organism. Wanting to make the same comparison made before, RNA behaves like a RAM memory: its structure is much simpler (DNA acts as a “template” for the RNA molecule, with the only difference represented by Uracil which replaces Thymine ), it is more delicate and the information is volatile. Once RNA does its job, it undergoes rapid degradation.
MRNA It is the messenger RNA, nothing more than that type of RNA that is essential for transferring genetic information from DNA to cell sites (ribosomes) where protein synthesis takes place.
The modRNA technology behind the BNT162b2 vaccine
To induce the production of certain proteins in a certain cellular context, scientists have been able to devise a “modified RNA” technology over the years. Růže It represents “Nucleoside-modified messenger RNAAnd it is exactly the type of genetic information present in the BNT162b2 vaccine in question. It is a laboratory-made mRNA molecule in which some nucleosides of the original sequence are replaced by modified natural forms or by synthetic nucleoside analogs. In the case of the vaccine in question, within the genetic sequence there is no nucleoside that contains uracil (letter U), but there is a synthetic “version” (1-methyl-3′-pseudouridine) identified with the Greek letter Ψ (psi).
The ultimate goal of the vaccine is to stimulate the immune system to produce antibodies against the aforementioned spike protein, without obviously inducing disease. Thanks to laboratory modifications, it was therefore possible to create a small segment of the genetic code (modRNA) that, by entering human cells without causing any damage or permanent modification of the DNA code, allows the same cells to produce a “modified spike protein”. ”Capable of activating the immune system. Once “exposed” to these new proteins, therefore, the body will quickly be able to produce antibodies capable of “countering” the modified protein in question and, at the same time, also the possible “original” spike proteins of the true coronavirus. own. In short, the vaccine does nothing more than “trick” the immune system!
Subjects who have already faced the disease, at least for the moment, do not need to carry out the vaccination because they already have all the necessary antibodies to avoid getting sick again. Although sporadic “double positive” cases have been reported, immunity from a previous SARS-CoV-2 infection must be ensured for a long time (months, if not years). Only in the coming months will it be possible to get an idea of the duration of the antibodies; This applies both to sick and cured subjects, as well as to all those who will be vaccinated (with, therefore, safe calls).
4,284 nucleotides in 6 different portions: here is the source code of the vaccine
For some time, all the information about the vaccine developed by BioNTech / Pfizer has been available and freely accessible. In addition to the results of clinical studies that speak, numbers in hand, of aefficiency of about 95% in the total count of administrations, the list of excipients is known, as well as the complete genetic sequence of the mRNA encoding the modified spike protein.
The following is the complete “source code” for the BNT162b2 vaccine:
The code is made up of 4284 nucleotides organized in 6 different “sections”:
- Cap: in position 1 and 2 there is the GA sequence, which acts as a “hood” for the rest of the information and indicates to the cell the “human” origin of the genetic sequence. Thanks to this small segment of code, the cell can “validate” everything and start reading and translating what follows. The sequence “cap” is more or less equivalent to what are the shabang of the UNIX systems (“#!”) And the MZ of the MS-DOS systems: they are not executable commands, but they must be there for everything to run which is in the queue.
- 5′-UTR: since position 3 to 54 there is a genetic sequence that is not translated into any protein but is “read” by the cell. It indicates the “upstream” position of the sequence (5 ‘, five minutes) and is a kind of compass to ensure the direction of translation. Translation occurs in the 5 ‘-> 3’ direction. In this section of the code the letter Ψ appears, replacing the U: after years of study it has been seen that by adopting this “trick” the organism is capable of accepting genetic information, considering it “not harmful”. In computing, viruses and malicious code use the same principle to confuse antivirus and firewall; in the case of the vaccine, however, everything happens “for a good purpose.”
- S.I.G: since position 55 to 102 there is the genetic sequence of the signal peptide of glycoprotein S. The genetic information embedded in it is what serves to guide the nascent protein (synthesized by ribosomes) through the endoplasmic reticulum until it leaves the cell. This code segment has the same function as that of the virus, with some structural changes in the triplet as to ensure the easy acceptance of the code by the body. Proteins are made up of amino acid sequences, which in turn are synthesized from the genetic code organized in codons: the “nucleotide triplet” code gives rise to 64 different combinations, enough to code for all amino acids. Some of them may be encoded by more than one codon. The principle is always the same: to fool the immune system, you have to make it believe that it is “harmless information” produced by the body. In this case, some letters have been replaced by others capable of producing – pass us the word – harmless “synonyms”. There should be nothing exogenous, apparently, in what the body reads and is going to produce.
- S protein_mut: since 103rd at 3879 that is the true heart of the vaccine, which is the optimized genetic sequence that will lead to the formation of the modified Spike protein that will serve to stimulate the immune system. The sequence is similar to that of the original virus: many triplets are replaced by “synonyms” but what makes the difference is the replacement of the amino acids Lysine (AAA) and Valine (GUU), which in the vaccine are converted into Proline (CCU ). What is all this for? Simply, taking the concept to the extreme, to prevent the newborn’s modified Spike protein from binding to any part of the body. In the virus, the Spike protein needs to be exposed outside the capsid / pericapsid; the vaccine does not need this feature, since it is sufficient for the modified Spike protein to be “free to circulate” to rapidly stimulate the immune system. At the end of this genetic sequence there are two UGA stop codons whereas the original virus uses only one in the UAA form. It is a type of safety mechanism that can pinpoint where protein synthesis ends.
- 3′-UTR: from position 3880 to 4174 we found the “downstream” analog of the 5′-UTR segment found earlier. Its function remains a mystery, but it is clear that it is a fundamental piece of code capable of ensuring the correct “direction” in reading information. Together with 5′-UTR it acts as a compass.
- poly (A): from positions 4175 to 4284 there is a sequence of 110 nucleotides that serve to protect the mRNA from easy degradation. There are 30 A’s (adenosine residues), followed by a nucleotide-like sequence consisting of ten “letters” (GCAUAUGACU) that precede another 70 A. Each mRNA can be reused by the body multiple times, gradually consuming the A’s in the end of the code; when A’s are “depleted”, the mRNA degrades. The 110 nucleotide solution is likely to be “proprietary” and ensures that the BioNTech / Pfizer vaccine is of adequate duration over time.
Just over 1 kilobyte for storage between -60 ° C and -86 ° C
No microchips, no 5G. In the newly arrived vaccine in Italy as well as in the rest of the European Union, of course, there is none of this and the few excipients present are extremely common. The vaccine must be stored at very low temperatures because the mRNA (or modRNA if you prefer) is extremely fragile and to ensure its efficacy it needs, during storage and transport, to remain in average temperature of -70 ° C, with a rank what can go -60 ° C to -86 ° C. The genetic information it contains “weighs” approximately 1 kilobyte, while that of the real virus reaches 7.5 kilobytes.
The development of the vaccine in question in such a short time, about 9 months, was possible thanks to the combination of many factors. SARS-CoV-2 belongs to a family of “simple” viruses known for many years and the knowledge gained from the earlier MERS and SARS viruses has contributed greatly to the development of the entire scientific basis from which all conception / realization processes. MRNA vaccines are not an absolute novelty, funding has come – conspicuous – from around the world and there is certainly no shortage of human volunteers.
We reiterate one of the concepts expressed at the beginning of this article: for the moment, the vaccine is the only weapon we have to combat SARS-CoV-2. At the time of writing, around four million people have been vaccinated worldwide and no deaths have been documented after the administration; In Italy, again as of December 27, 2020, the officially registered cases of Covid19 disease are approximately 2.05 million, with a total death count directly approaching 72 thousand.
Editor’s note: Vittorio Romano Barassi He has a degree in Medicine, and even though he regularly reviews smartphones, he has the right to write such content at a time when information about vaccines is not always correct.
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