The hypothesis is that Covid-19 is caused by a viral infection followed by a bacterial disease probably due to a symbiosis between the two agents. From stage 1, this synergy between the two agents is established and contributes to the long development of the disease, explaining the atypical nature of the symptoms.
Viruses and species
Beta-coronaviruses infect many animal species, not just pangolins and bats that were discussed recently when the new Wuhan virus first appeared, n-CoV-2019 now known as SARS-CoV-2. SARS first in 2003 responsible for acute respiratory syndromes that caused nearly 800 deaths worldwide before being stopped.
There are four kinds of coronaviruses among which we find the CCoV which is of the genus alpha, infects the dog, causing diarrhea and against which a vaccine is available. This virus was discovered in 1971 in a watchdog farm. Viruses are intended to remain within the species that hosts them, but on rare occasions, an inter-species transfer occurs. Until the 1970s, virologists believed that a virus does not cross the barrier between species, then discovered that human flu could pass to pigs, cats, poultry and vice versa.
Recombinations of genetic material are strongly suspected of creating new viruses when double contamination occurs. And if this virus is viable in one of the species, then a new epidemic emerges. This is what probably happened during the 2003 SARS epidemic and now Covid-19. For inter-species migration to occur, there must be promiscuity, and it is for this reason that cohabitation between farm animals and humans is strongly suspected of favoring the emergence of hybrid viruses. It is therefore important to understand how a virus enters an organism
The Spike protein, the key to entering the cell
To replicate, a virus must enter the host cell and to do this, it must have a molecular arsenal allowing it to first attach to the cell membrane, then to penetrate inside. Otherwise, you need a key to open the cell door and a mechanism to push the door in and out. This image including a very rough idea of the subtlety of molecular techniques (as it is) used by these pathogens. The two SARS have in common the use of a transmembrane glycoprotein S composed of three monomers (it is a trimer, made of three pieces). Each monomer is of a more than respectable size, consisting of more than 1000 amino acids.
The complete protein is broken down into two parts with distinct functions. The N-terminal part binds to the ACE2 membrane receptor, the lock, so to speak. The other part fuses with the membrane of the host cell which allows the virus to pass to the other side of the membrane. It is as if a drug smuggler arrives in the control zone, sticks to the customs officer and begins to take a few waltz steps, then releases him and continues his course freely in the airport zone.
In reality, it is very complicated, it is necessary for a protease to cut the Spike protein so that the genetic material can reach the interior of the cell to reproduce. The virus must peel off the customs membrane to finish its course and smuggle its stock of information inside the cell.
The virus searches for keys and codes
The Spike protein is the key to the virus. This key is used to enter specimens of the species that harbors the virus, bats, pangolin, dog, civet, mouse, human, etc. But as the virus mutates, it tends to seek to force other locks. In reality, we will soon know that the image of the key is not suitable while that of the digital code is more appropriate. Or even a frequency that opens a door to the image of electronic keys used for cars.
The virus sometimes looks for codes to enter the cells of other species and sometimes it does so by mutating. It is this mechanism which has been explained in numerous studies like this one establishing that the extension of the domain of infection of a murine coronavirus rests on the variability of the N-terminal domain of the protein Spike.
“Although murine coronaviruses naturally infect only mice, several virus variants derived from persistently infected murine cell cultures have an extended host range. The mouse hepatitis virus (MHV) variant MHV / BHK can infect hamster, rat, cat, dog, monkey, and human cell lines”JH Schickli
This means that the entry of the virus into the species it is not used to infect rests on the N-terminal domain which in the end has become a sort of pass allowing to crack the locks of other species . This is the case of the MHV / BHK variant. The initial MHV strain only infects murine cells. The BHK variant is characterized by a variation of amino acids in the N-terminal part of the Spike protein whose other domain allowing fusion is much more conserved.
This logic of viral keys has been seen for other coronaviruses and in particular the SARS-CoV of 2003. For the virus of 2019, the results are still incomplete. But we will see later that this Spike protein deserves our attention because it undergoes notable variations.
The logic of the virus is easy to understand. To enter a cell for which he does not have codes, he must try all the possible codes, even if it has to mutate and if that does not work, he will steal the codes allowing to infect other species and it looks very recombination. In other words, the virus is a system that tries to crack the access codes present on the membranes of host cells. These codes are reserved for molecules and transfers that the healthy body uses to function. This time, I drop the mechanical image of the key to use the image of the code, an image that works in the new science which is biosemantics .
From SARS to SARS CoV-2
Travel under the wings of a bat . The combination of genomics and bioinformatics makes it possible to trace similarities or even differences between several viruses. A recent article compared the two SARS responsible for the epidemics of 2003 and 2020. The authors placed the spotlight on the preserved sequences. For my analysis, I will do the opposite.
The most important differences concern the wNsp3 domain and the S domain. Nsp3 is organized into 6 subdomains, it codes for a megaprotein which is a protease, one of the functions of which is to machine the different parts of the polymerase used to replicate the genome. From there to explain the difference between the two SARS, I will not take the step. On the other hand, the domain S is more interesting. The authors noted the presence of four specific insertions for SARS-CoV-2, absent on SARS-1.
This means that the new virus uses other codes. These four insertions were absent from close coronaviruses isolated from bats in 2015 and 2017 ; on the other hand, a bat virus isolated in 2013 contains these four insertions. SARS-CoV-2 may well have ” stolen ” old codes. The part of protein S that has mutated the most is that which interacts with the ACE2 receptor. The new virus therefore uses the same receiver as the old one, but it seems to have new codes. To do what ? To sneak into cells, no doubt, but which cells ?
The models carried out on the interactions between proteins (the interactome) show that the intra-viral interactome concerning the replication mechanisms inside the cell is much more conserved than the interactive network concerning the interaction between the virus and l ‘host.
This fact was already known and shows the great plasticity available to viruses to infect host cells. In other words, a little variable machine for replicating a virus and a mechanism for entering the cell with significant variability. The last point seems anecdotal but intriguing. It is the almost perfect conservation on the surface of Nsp3 of a binding site on a human protein functioning with ubiquitin-aldehyde. This protein (OTU) is known to regulate transcription as well as for its interaction with mechanisms involving steroid hormones.
A link between SARS-CoV-2 and bacteria
The virus seems to have many codes. Could it interfere with bacteria ? Before answering this question, it is necessary to mention a fact passed under the media radars. The bacteria have been identified in patients with advanced or severe forms of Covid-19 and among microbes is prevotella .
This prevotella bacteria
A regular in the human microbiota, certain strains of which can cause problems in the respiratory tract. It causes disorders in the upper respiratory tract, especially in chronic sinusitis. A detail is important. Anosmia has been observed in a number of patients with Covid, from stage 1 and more often in stage 2. However, affections in the sinuses caused by prevotella also cause anosmia.
Is age related also due to prevotella bacteria ? Yes if we believe this study conducted on infections in the maxillary sinuses where anosmia and ageusia are present : ” Decreased smell can be divided into partial hyposomia and total anosmia , which are both related to anterior ethmoidal mucosal opacifications .
Sometimes such patients complain of reduced taste sensation, known as ageusia. ” The prevotella bacteria has been identified in this condition
“WHO has basic polymicrobial characteristics, with predominantly anaerobic bacteria in both the oral cavity and upper respiratory tract. Aerobic Staphylococcus aureus and Streptococcus pneumonia (S. pneumonia) and anaerobic Peptostreptococcus and Prevotella spp . are found in more than 75% of cases”S. Min Kim
Let’s continue looking for clues. A prevotella strain causes rheumatoid arthritis. ” For example, a study has revealed intestinal dysbiosis in newly diagnosed patients, characterized by an excess of Prevotella species, in particular P. copri ” As luck would have it, chloroquine used against arthritis seems to have a modest but not decisive effect on Covid-19. To this element is added the presence of a ” cytokine storm ”
” This phenomenon of” hyper-inflammatory storm “has been identified and described for only twenty years. He was singled out to explain the danger of two other respiratory diseases caused by coronaviruses, SARS (774 died mainly in Asia in 2002-03) and Mers (Middle East respiratory syndrome, 866 deaths since 2012).
He is also suspected of having been at work during major influenza pandemics, such as the terrible “Spanish flu”, which killed around 50 million people in 1918-19. “(Science and future, 04/04/2020). Studies have shown that the Spanish flu was severe due to a bacterial complication. In addition, this storm of cytokines is also the sign of a bacterial infection which once again goes through some mystery under the radars of specialists.
There remains one last cartridge to play, this unique publication on a possible infection of the bacteria prevotella by SARS-CoV-2 which would then be more cunning than we think and would behave like bacteriophage, which could explain the modification of this bacteria, becoming more aggressive. As well as abnormalities observed on the viral load, as if the virus was hiding in the bacteria.
Obviously, this data cannot enter into the argumentation for lack of additional studies carried out by the virologists. In support of this hypothesis, SARS-type coronaviruses are capable of modifying the membrane permeability of bacteria E. See this reference :
Another detail, this study showing a link between intestinal microbiota and coronavirus : ” We also found that coronaviruses receptors could be elevated in the presence of both invasive bacteria and their counterpart, probiotics. We demonstrated here that enterocytes act as a conserved cell reservoir for coronaviruses during their evolutions, which should not be ignored in the investigation of coronavirus diagnosis and treatment strategies. ”
We now have the clues to a disease
Covid-19, whose affections have a double origin, viral and bacterial, and this, sooner than we think, in other words, well before stage 2 then 3 and bacterial complications observed and known for a long time . A sort of atypical duo played by two microbes.
There are therefore two agents that combine to infect patients with Covid-19. It seems that an undoubtedly unknown interaction means that viruses and bacteria, notably prevotella , seem to interact. As if the bacterium had used the viral genome to modify itself, whereas this same genome uses the bacterium to stay, even hide, which explains the jokes in the analysis of viral load. In other words, there would occur, very early, a symbiosis between bacteria and the SARS-CoV-2 virus which would complement each other to infect and attack the patient. It’s fairly new, but that’s how science advances.
The atypical development of this disease, with ups and downs, may well be linked to this double invasion, or at least a first phase of viral infection which, once in the body, activates the bacteria which launch a second attack. . The development of the disease is consistent with a double infection, a double set of two accomplices. This second phase would be present from stage 1. And therefore, it would not be chloroquine but azithromycin which represents the first therapeutic principle. And it should then be administered from stage 1, when the symbiosis virus bacteria begins. It’s to be tested, without using chloroquine
The bacterium prevotalla is it part of the sensitivity spectrum of azithromycin ?
The answer is yes. This would explain the effect of azithromycin in the results of Didier Raoult on the reduction of viral load. FYI, this antibiotic has fallen into the public domain, laboratories around the world produce it and market it in generic form.