Background: Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of the chemical substance NIOCH-14 and its safety and bioavailability in the body of laboratory animals. Methods: The safety of NIOCH-14 upon single- or multiple-dose intragastric administration was assessed according to its effect on the main hematological and pathomorphological parameters of laboratory mice and rats. In order to evaluate the pharmacokinetic parameters of NIOCH-14 administered orally, a concentration of ST-246, the active metabolite of NIOCH-14, in mouse blood and organs was determined by tandem mass spectrometry and liquid chromatography. Results: The intragastric administration of NIOCH-14 at a dose of 5 g/kg body weight caused neither death nor signs of intoxication in mice. The intragastric administration of NIOCH-14 to mice and rats at doses of 50 and 150 µg/g body weight either as a single dose or once daily during 30 days did not cause animal death or critical changes in hematological parameters and the microstructure of internal organs. The tissue availability of NIOCH-14 administered orally to the mice at a dose of 50 µg/g body weight, which was calculated according to concentrations of its active metabolite ST-246 for the lungs, liver, kidney, brain, and spleen, was 100, 69.6, 63.3, 26.8 and 20.3%, respectively. The absolute bioavailability of the NIOCH-14 administered orally to mice at a dose of 50 µg/g body weight was 22.8%. Conclusion: Along with the previously determined efficacy against orthopoxviruses, including the smallpox virus, the substance NIOCH-14 was shown to be safe and bioavailable in laboratory animal experiments.
This article has been retracted.It has been brought to the attention of the journal that ergoferon in 'Activity of ergoferon against lethal influenza A (H3N2) virus infection in mice' is an antibody preparation in homeopathic concentrations that was not so described in the manuscript.The journal does not consider articles reporting on homeopathic products or highly diluted preparations and would normally have rejected it had it been described as such in the manuscript.
Introduction. Influenza A virus is the cause of epidemics and pandemics that severely affect the health and socioeconomic status of the world's population. The need to develop new methods of etiotropic therapy, and the increasing ability of viruses to counteract the antiviral drugs makes extremely relevant the search for new pharmacologically active substances and the subsequent study of their medicinal properties.The aim of the study is to conduct research into the antiviral properties of melanin obtained from the pharmaceutical chaga mushroom in relation to different subtypes of the influenza A virus.Materials and methods. A sample of water-soluble melanin from Inonotus obliquus obtained by alkaline hydrolysis and dried at 40C was tested for toxicity and antiviral activity. The commercial anti-influenza drug Tamiflu was used as a reference drug. Statistical processing of the obtained data was carried out according to the Spearman-Kerber method.Results. Inonotus obliquus melanin (sample 20-24) toxicity markers, such as a maximum tolerable concentration (MTC) of 237.0 g/mL, and a 50% cytotoxic concentration (CC50) of 153,45 g/mL were established for MDCK cell culture. The assessment of antiviral activity of test sample against three subtypes of the influenza A virus (H5N1, H3N2 and H1N1pdm09) demonstrated a decrease in the infectivity of the influenza virus by 2.53.5lg with 50% virus-inhibiting concentrations (IC50) of 1.559.52g/mL. Based on the obtained values of CC50 and IC50, the selectivity indices (SI) of the sample were calculated, characterizing its prospects for further research.Conclusions. Melanin obtained from the pharmaceutical chaga mushroom showed the highest activity against the strain of the human pandemic influenza virus A/California/04/2009 (H1N1)pdm09, caused a decrease in its infectivity by 3.5 lg and had an IC50 of 1.6 g/ml. The obtained results indicate the prospects for creating an antiviral drug based on Inonotus obliquus melanins against the influenza virus.
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