Use of bioassimilable boron compounds for the control of subviral pathogenic agents
The use of bioassimilable boron compounds is disclosed. The object of the invention is a new use of bioassimilable boron compounds. Boron compounds are used to prepare a medicament for fighting subviral particles that cause subacute, degenerative, non-inflammatory diseases of the central nervous systems in animals and humans or for protecting plants against the action of subviral pathogenic agents. The boron compounds can also be used in combination with bioassimilable silicon or copper compounds.
Description
The invention relates to the use of bio-assimilable boron compounds.
Viroids are infectious particles that replicate autonomously in adequate host cells. They represent the smallest form of life. With subviral dimensions of approx. 10 x 1 nano-esters, the rod-shaped structures are smaller than the most primitive virus. They consist of an annular molecule of rbonucleic acid: 246 to 375 nucleotides are single-stranded and covalently closed to form a tertiary structure of high stability, 2/3 of the opposite bases being complementarily paired. Open-chain, simple and multiform shapes also occur. Viroids are not surrounded by their own viroid-specific protein envelope. Up to now, viroids have only been isolated as particles from the cells of higher plants, but infectious ribonucleic acids of the same type have also been detected in certain diseases in vertebrate cells.
In addition to the absence of cellular structures, a property that they share with the viruses, these smallest parasites are characterized by the fact that they do not encode proteins. They leave no fingerprint in the protein machinery of the invaded cell and escape on the antiviral defense mechanisms of the infected host organism, at least during the incubation.
Viroids do not cause active or passive resistance in plants. They do not induce hyperergic reactions or the production of antivirus proteins.
Incubation times are orders of magnitude longer than with viral infections. They can be many years for long-lived plants. However, high temperatures (tropical climate) drastically shorten the latent periods.
Injected into mammals, viroids do not cause an immune response, in contrast to all viruses, including plant viruses. They do not induce interferon production. There is no serological reaction. The pathogenicity of the viroids lies beyond the classic definition of the infectious diseases of Pasteur and Koch.
The immunogenic differences between the two types of pathogen are related to the fact that viruses cause transcriptional diseases, whereas viroids cause post-transcriptional ones.
Viruses primarily regulate the synthesis of cellular proteins and encode their own virus proteins in their place, which leads to an immediate immune response in the mammalian organism. Due to their relative size as particles and their protein and / or glycoprotein coating, classic viruses are the model for a potential antigen. Viral proteins are presented on the Hista compatibility molecules of class I (MHC I).
Viroids and viroid-analogous pathogens, however, only use the host's proteins. This and her small From the outset, any presentation as an antigen and the subsequent immunogenic reaction are excluded.
The metabolic harmful effects of the viroids start relatively late due to post-transcriptional disturbance of the host's own protein and glycoprotein cycle. Under the action of the viroids, they experience:
- alienation of functions
- Disability of transmembrane transport
- blocking of the dismantling
- Protein polymorphis as a result of incorrect processing.
This leads to concentration-like accumulations of non-transferred, non-recycled and possibly processed host proteins in stagnating cellular or intercellular pools, where they become invulnerable to proteinases with crystallization, mineralization, fibrillization and / or amyloid plaque formation and irreversibly reach the deposit. The viroid-related malfunction of the body's own proteins only allows the immune system to use auto-immune antibodies, and this in a later phase after the accident has become irreversible, ie. H. in the final stages of the disease. Indeed, in the late lethal stages of subacute diseases in mammals caused by void-like particles, autoimmune antibodies are found which are directed against the crystallized host proteins. In mice, an influence of the class II (MHC II) Hista compatibility genes on the course of the infection was determined. The spongy perforation of affected nerve tissue as a result of inflammation-free, spontaneous cell destruction is reminiscent of apoptotic self-extinguishing mechanisms of the cells, which can be triggered by autoimmune signaling.
Their primitiveness and their sequential, genomic proximity as well as their complementarity to functional host cell ribonucleic acids (introns, 7S-, 7SL-RNAS, ribonucleases P and L) has Viroid and assimilated infectious particles have so far been removed from any selective curative influence, because any targeted action on the viroid parasite affects essential host cell functions.
Of all parasites, the functional proximity to the normal constituents of the host cell is greatest in the case of viroids and other subvirous molecules, which leads to the expectation of maximum difficulties in their identification and control from the outset.
Viroids from plant cells can be isolated as a single structure and are visible under electron microscopy. Blot methods are highly sensitive and allow one viroid to be detected per cell.
In the animal and human areas, however, it has so far not been possible to screen and isolate disease-specific, viroid-analogous ribonucleic acids found in infectious tissues in free form as unpackaged, autonomously operating particles. Under the physiological conditions of the animal cell, ribonucleic acids are still protein-packed on the strand that forms during transcription, replication and "processing". Specific binding affinities for molecules of the host cell resist the existence of naked RNA viroid particles. In addition, the body temperatures prevailing in warm-blooded hosts favor the dissolution of possible autonomous structures of animal viroids. At 38 ° C, plant viroids are also already in molten modifications that are active in the attachment.
The energies occurring in intermolecular associations are greater than those which can be obtained by actuating the still available intramolecular, self-complementary base pairings (1.2 kcal / nucleotide pair). The complexes are more stable than the viroid particle in itself. Viroid-like pathogens in animal cells are located per nent in the ecliptic state. Their transmission with the aid of the infected cell material does not require the formation of individually packaged, visible particles as in the case of viruses, which would already fail because of the low coding capacity of such viroid and other subvirous RNAs.
Specific intermolecular bonds of subvirous RNAs exist to host-cellular nucleic acids (anti-sens RNA segments, anti-genomic binding), to lipids (phospholipids) and to the enzymatically and physically highly resistant, fibrillar or amyloid pathogenic protein Associates. The exciters are packaged and masked. The association becomes biologically indestructible through the mutual stabilization of its components.
Fibrillar and aoid protein aggregates form in stagnant pools, with the presumed participation of the viroid parasites. It happens u. a. on post-transcriptional point mutations of host-coded, normally not pathogenic proteins: At certain positions, hydrophilic amino acids are substituted by lipophilic and acidic ones by basic amino acids. Some authors even attribute auto-replicative properties to the bundled, pathogenic, highly resistant prion protein aggregates.
At the same time, the affinity for basic microscopic stains (basophilic character) increases in the affected neurons.
A strong lipophilic affinity of the pathogens or their associates helps to avoid defense reactions from the aqueous-serological environment. The switch to the lipophilic milieu is also expressed in the preference of the pathogens for lipid-rich tissue in the invaded host: brain, nerve tracts, spinal cord, pituitary gland, spleen, eyes, lymphocytes, intestinal tract and all secretory tissues are the main target organs. Pathogens in such infectious tissues can be inactivated by treatment with lipophilic solvents (acetone). Plaques and fibrils of the prion proteins can be resolved by the successive action of nucleases and proteinase K.
While the replication cycle of viroids in plant cells has been elucidated, the activity of viroid-like particles in animals and humans is still largely unknown.
However, the high infectivity of all types of viroids and the virtually indestructibility of the viroid particles are known. In contrast to bacteria and viruses, they can practically no longer be removed from a contaminated habitat and lead to cumulative biocontamination.
This results in the considerable economic importance that must be assigned to the non-destructive control of viroid infections in plants and animals.
In animal and human areas, viroid-like particles and viroid segments integrated in viral genomes are associated with a number of degenerative, non- or post-inflammatory diseases of the central nervous system. After long incubation periods and latency periods, they can lead to severe neuropathological disorders and from then on they are always fatal. Viroid-like parasites in mammals and in humans are causally or as a co-factor associated with approximately 50 subacute-chronic diseases.
Viroid and assimilated infectious particles are characterized by an exceptional physical, chemical and biological resistance.
The inactivation by UV, ionizing and neutron radiation, by heat, formaldehyde and alcohol and by nucleases and proteinases has only a limited effect.
(...)
Alternatively, some of the plants were also enriched with bio-assimilable silicon (neutralized water glass). It was found that silicon extends the normally narrow boron tolerance limits of the plants: the toxic effect of the boron compounds is shifted to considerably higher concentration ranges. Plant-available silicon acts, so to speak, as an antidote against the herbicidal effects of large amounts of boron compounds.
It should be noted that silicon without boron, like all other trace elements tested to date, stimulates the virulence of the viroid infection and accelerates the death of the plants.
In order to ensure the effect according to the invention and to differentiate it from the existing state of the art, a number of additional experiments were undertaken. It was confirmed that it is a selective effect which is not based on an unspecific, general increase in the natural resistance of the plant through a sufficient supply of the trace element boron necessary for it.
1.
This is shown by the fact that other trace elements tested to date (eg manganese, silicon), which are also known to improve the growth and resistance of the plant, act in the opposite direction, ie increase the pathogenic action of the viroids, and that only boron selectively exerts the protective effect described.
2. The fact that boron-protected, infected plants produce more biomass than only boron-enriched control plants without a viroid shows that something is happening that cannot be combined from the previous state of knowledge. Since the infected plant first has to provide the synthesis performance for up to 20,000 viroid particles per cell and then has to suffer its pathogenic effect, starting from the existing state of the art, its biomass production should in any case be significantly lower than that of the uninfected control plants.
3. The dosage of the viroid particles in the infected plant material by molecular hybridization and Northern blot surprisingly resulted in a 5 times higher viroid concentration for the boron-protected plants than in the control plants with the normal boron content. The viroid is present in the cells of the boron-protected plants and in high concentration, but it has become unoffensive for the plant.
The protective effect is therefore not based on a simple nutritional strengthening of existing plant defenses directed against viroid replication, but on a modification of the pathogenic properties of the parasites. A distinction must be made between infectivity (number of infectious particles), which increases, and pathogenicity (extent of cell destruction), which is neutralized. Boron compounds cause the formation of non-pathogenic viroid strains, which may even have auxiliary functions in host cell metabolism (more biomass), which is an indication The origin and origin of the viroids would have to be assessed: in the very likely case that viroids are evolutionarily derived from normal, cell-specific RNA, which has gotten out of control, the action of boron would reverse the degenerative process, ie a return transfer of virous ones RNA segments in the direction of normal, constructive cellular functions mean.
Boron seems to cause the formation of thermodynamically stable viroid base bodies with a low tendency to form loops and a strongly delayed melting behavior (= intramolecular resolution of pairing).
Stable viroid modifications only melt at elevated temperatures. However, in order to develop its pathogenicity and to obtain a broad host spectrum, the viroid molecule requires pronounced tertiary structures with easy, rapid and numerous formation of loops and branches even at temperatures of the infection, which specifically attach to factors of the host cell enable.
The favoring of stable viroid strains with difficult melting behavior by the boron explains, at least in part, its anti-pathogenic effect on the viroids.
The use of bioassimilable boron compounds is disclosed. The object of the invention is a new use of bioassimilable boron compounds. Boron compounds are used to prepare a medicament for fighting subviral particles that cause subacute, degenerative, non-inflammatory diseases of the central nervous...
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