Antiviral Activity of Some Compounds of Gasteroid Mushrooms from Western Siberia.

The antiviral activity of aqueous and ethanol extracts from the fruiting bodies of gasteroid Basidiomy-cetes of Western Siberia: Lycoperdon pyriforme, Lycoperdon perlatum, and Phallus impudicus, as well as an aqueous extract from cultivated mycelium of P. impudicus and total polysaccharides from it, on MDCK cell culture against influenza A virus, was studied. Aqueous and ethanol extracts from the fruiting bodies of all studied gasteroid fungi showed antiviral activity against human influenza virus A/Aichi/2/68 (H3N2) and bird A/chicken/Kurgan/05/2005 virus (H5N1). At the same time, extracts from P. impudicus and L. pyriforme showed more pronouncing antiviral activity compared to the activity of the reference drug Tamiflu against the A/H5N1 avian influenza virus. A high antiviral efficacy of an aqueous extract from cultivated mycelium of the P. impudicus and a sample of total polysaccharides from this extract against the A/H5N1 avian influenza virus was revealed.

Substantial Antiviral Potential of Deoxyribozymes Fixed on Anatase Nanoparticles Against Influenza A Viruses in vitro and in vivo.

Influenza A viruses (IAV) are a high threat to humanity because of a lack of proper effective antiviral drugs and resistance of viruses to existing vaccines. We describe the sufficient anti-IAV effect of Ans/PL-Dz nanocomposites that contain deoxyribozymes (Dz) immobilized on anatase TiO2 nanoparticles (Ans) through polylysine linker (PL). The Dz-containing nanocomposites appear to be more efficient than the Ans/PL-ODN nanocomposites that contain common oligodeoxyribonucleotides (ODN) targeted to the same RNA regions of the viral genome. The simultaneous use of nanocomposites that contain Dz and ODN, which are targeted to different sites of viral RNA provides a higher overall effect than the independent action of each of them (synergism). The inhibition of IAV with the proposed nanocomposites was shown to be effective, sequence-specific, and dose-dependent. The most efficient Ans/PL-Dz nanocomposite exhibited a high antiviral effect in vivo on mice models. The efficiency of IAV inhibition with this nanocomposite in vitro and in vivo is higher than that for the approved antiflu drug oseltamivir. The results open the prospect of creating a unique antiviral agent suitable for IAV suppression.

Safety and Pharmacokinetics of the Substance of the Anti-Smallpox Drug NIOCH-14 after Oral Administration to Laboratory Animals.

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.

Activity of ergoferon against lethal influenza A (H3N2) virus infection in mice.

BACKGROUND: The influenza A virus accounts for serious annual viral upper respiratory tract infections. It is constantly able to modify its antigenic structure, thus evading host defence mechanisms. Moreover, currently available anti-influenza agents have a rather limited application, emphasizing the further need for new effective treatments. One of them is ergoferon, a drug containing combined polyclonal antibodies - anti-interferon gamma, anti-CD4 receptor and anti-histamine - in released-active form. The purpose of the study was to assess ergoferon antiviral efficacy in mice challenged with the A/Aichi/2/68 (H3N2) influenza virus. METHODS: The virus was inoculated intranasally at a 90% lethal dose. Ergoferon was administered at 0.4 ml/day per os in a preventive and therapeutic regimen - daily for 5 days prior to and for 16 days after the challenge. The reference product, Tamiflu (oseltamivir), was used as a positive control treatment - at 20 mg/kg/day for 5 days after the challenge. Mice in the negative control group received distilled water which had been utilized for test sample preparation; untreated control animals received no treatment. Antiviral efficacy was assessed by an increase in survival rate, average life expectancy and virus titre reduction in the challenged mouse lungs. RESULTS: Survival rate and average life expectancy values were increased significantly in groups treated with ergoferon and Tamiflu, as compared with controls. Lung virus titres were reduced in these groups as observed on days 2 and 4 post-inoculation. CONCLUSIONS: Ergoferon demonstrated antiviral activity by reducing the severity and duration of the major signs of induced influenza infection.

New effective chemically synthesized anti-smallpox compound NIOCH-14.

Antiviral activity of the new chemically synthesized compound NIOCH-14 (a derivative of tricyclodicarboxylic acid) in comparison with ST-246 (the condensed derivative of pyrroledione) was observed in experiments in vitro and in vivo using orthopoxviruses including highly pathogenic ones. After oral administration of NIOCH-14 to outbred ICR mice infected intranasally with 100 % lethal dose of ectromelia virus, it was shown that 50 % effective doses of NIOCH-14 and ST-246 did not significantly differ. The 'therapeutic window' varied from 1 day before infection to 6 days post-infection (p.i.) to achieve 100-60 % survival rate. The administration of NIOCH-14 and ST-246 to mice resulted in a significant reduction of ectromelia virus titres in organs examined as compared with the control and also reduced pathological changes in the lungs 6 days p.i. Oral administration of NIOCH-14 and ST-246 to ICR mice and marmots challenged with monkeypox virus as compared with the control resulted in a significant reduction of virus production in the lungs and the proportion of infected mice 7 days p.i. as well as the absence of disease in marmots. Significantly lower proportions of infected mice and virus production levels in the lungs as compared with the control were demonstrated in experiments after oral administration of NIOCH-14 and ST-246 to ICR mice and immunodeficient SCID mice challenged with variola virus 3 and 4 days p.i., respectively. The results obtained suggest good prospects for further study of the chemical compound NIOCH-14 to create a new smallpox drug on its basis.