Influenza virus treatment

Treatment via chelation has been observed for 2-acetylpyridine thiosemi-carbazone derivatives, which have been found to possess inhibitory activity for the RNA-polymerases of the influenza virus [133]. The iron(III) complexes were shown to be 3 to 6 times more active as inhibitors of partially purified ribonucleotide reductase (no added iron) compared to uncomplexed thiosemi-carbazone [128]. Raina and Srivastava [134] prepared and characterized low spin iron(III) complexes of 2-acetylpyridine thiosemicarbazone, [Fe(8-H)2A] (A = NO3, OH, Cl, N3, NCS or NO2), which were proposed as being seven-coordinate. However, all but the azide complex are 1 1 electrolytes in DMF and their solid ESR spectra are rhombic with the g-values being about 2.20,2.15 and 2.00. Of the six complexes, the azide ion seems to interact ihost strongly with the iron(III) center. 

Influenza viruses A and B can cause pneumonia in pediatric and adult patients. Amantidine and rimantidine are available oral agents with activity against influenza virus type A. If started within 48 hours of the onset of the first symptoms, they reduce the duration of the illness by about 1.3 days. Oseltamivir and zanamivir also are oral agents and are active against both type A and B viruses. These agents also reduce the duration of the illness by about 1.3 days if initiated within 40 to 48 hours of the first symptoms.29 For active infection beyond the first 48 hours, none of these agents is effective in treating the infection, and supportive care is the best treatment for these patients. 

It had been known since 1941 that red blood-cells are agglutinated by fluids containing influenza virus. In 1942, G. K. Hirst proved that purified influenza virus is quickly and quantitatively adsorbed on red cells, but that, after the elapse of several hours, the virus particle, apparently intact, has come off the surface of the red cells. After this treatment, cells were unable to be agglutinated by influenza virus or to adsorb virus particles. The problem of the interaction of influenza virus with red cells was attacked in a comprehensive manner by Sir Macfarlane Burnet and his coworkers in Melbourne in the period of... 

Sample preparation. All allantoic fluid of chicken embryos or calf serum used in experiments contained influenza virus (104—106 EID50/ml). The samples of biological fluids underwent photodynamic treatment as described above. One milliliter aliquots were taken before treatment and at 3 and 6 h after the start of experiment. To analyze the effect of photodynamic treatment on proteins we used alkaline denaturing electrophoresis in the presence of sodium dodecylsulfate (SDS) and P-mercaptoethanol (P-ME). 

As a result of our experiments, it was shown that the growth properties of the serum do not change after photodynamic treatment. Nevertheless, the infectious titer of influenza virus both in blood serum and allantoic fluid decreased from 6 to 0 log10 EID50 after the treatment. This fact suggests a selectivity of photodynamic treatment regarding the virions. In our opinion, this can be explained by the following. 

Currently, two classes of drugs are available with antiviral activity against influenza viruses inhibitors of the ion channel activity of the M2 membrane protein, amantadine and rimantadine, and the neuraminidase inhibitors oseltamivir, and zanamivir. H5N1 viruses isolated from poultry and humans in Thailand and Viet Nam in 2004 invariably showed an amantadine-resistance indicating that amantadine treatment is not an option during the ongoing outb-treak in South-East Asia. 

Influenza virus resistant to oseltamivir has not been found in naturally acquired isolates but has been isolated from influenza patients who have undergone treatment with this drug. These resistant strains contain mutations in the active site of neuraminidase and are generally less virulent and infective than nonresistant virus. In vitro passage of influenza virus in the presence of oseltamivir carboxylate can produce mutations in hemagglutinin that decrease the overall dependence of viral replication on neuraminidase however, the clinical relevance of this resistance mechanism is unknown. 

Phosphonoformate is a pyrophosphate analog and inhibits both DNA polymerases and reverse transcriptase. However, toxicity may prevent longterm treatment of AIDS patients. Amantadine has a narrow antiviral specificity. It specifically inhibits initiation of the replication of influenza virus RNA of type A (but not of type B). Active only against retroviruses, 3 -azidothymidine is a reverse transcriptase inhibitor, which acts by a chain termination mechanism. It was synthesized in the early 1960s but only recently has been used in treatment of AIDS victims. More recently a series of 2, 3 -dideoxynucleosides, such as dideoxyinosine, have also been used.d Acyclic phosphonates, such as phosphonylmethoxypropyladenine, avoid the need for metabolic phosphorylation of the drug.6... 

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