[The anti-viral activity of the complex glycyrrhizic acid-alpha-glutamyl-tryptophan against experimental lethal influenza infection in white mice caused by oseltamivir-resistant strain of the virus].

Influenza virus is a leading causing factor of infectious respiratory human pathology. The ability to implement the antigenic drift and development of drug resistance makes it important to develop novel anti-influenza drugs of wide spectrum of activity. In this work, we present the results of the study of the activity of a combination of glycyrrhizic acid with dipeptide alpha-glutamyl-tryptophan against oseltamivir-reistant strain of the virus Al Vladivostok/2/09 (H1 N1) on the model of lethal influenza infection in white mice. Application of Orvilax was shown to decrease the specific mortality of animals (index of protection 39-67% depending on the dose of the virus and drugs combination), to increase the mean day of death to 3.7-5.0 days and decrease the infectious titer of the virus in lung tissue to 1.3 Ig EID50/20 mg. The corresponding figures for the reference compound Tamiflu were 8-11%, 0.5-1.5 days, and 0.6 Ig EID50/20 mg. The use of Orvilax also led to reliable increase of the titers of interferon in the blood from 30.4 to 56.5 ME/mL. The results obtained allow the drug to be considered as a promising anti-influenza remedy that is active against the drug-resistant virus strains.

[Ingavirin treatment of experimental parainfluenza pneumonia in Syrian hamsters].

Parainfluenza viruses affect the upper respiratory tract in all age group patients, in children aged 6 months to 3 years in particular. The most urgent task is to design drugs to treat parainfluenza. This investigation studied the antiviral activity of Ingavirin (2-(imidazole-4-yl) ethanamide of pentandioic-1,5 acid) on a model of parainfluenza infection in Syrian hamsters. The drug was shown to restrict the infectious process in animal lung tissue. This restriction manifested itself as reductions in the infectious titer of parainfluenza virus in the lung tissue, in the degree of pulmonary edema and tissue cell infiltration, and in virus-specific lesion of bronchial epithelial cells. The in vitro experiments demonstrated the ability of Ingavirin to diminish the infective activity of viral descendants. The finding allows one to consider Ingavirin to be a promising antiviral agent that is active against parainfluenza infection in vivo.

[In vitro and in vivo effects of ingavirin on the ultrastructure and infectivity of influenza virus].

The aim of this investigation was to study the effect of ingavirin on the structure and properties of influenza virions forming in its presence. The infectious activity of the virus and the morphology of the virions were analyzed by titration in cell culture and electron microscopy, respectively. The use of ingavirin was shown to reduce the proportion of morphologically intact virions and to increase that of filamentous and giant particles. No defects of surface glycoproteins were observed. The effect of the drug did not depend on the chosen model of virus replication and it was similarly shown in both cultured human cells and laboratory animals. In MDCK and A549 cells and in the mouse lungs, viral infectious activity was decreased by 1-2 orders of magnitude in relation to a model. The findings suggest that Ingavirin is able to impair the processes of viral morphogenesis, which in turn leads to a reduction in the infectivity of progeny virions.

[Antiviral activity of Ingavirin on an animal model for experimental disseminated adenovirus infection].

Adenoviruses constitute a clinically important family of human pathogens. Due to their wide tissue tropism, adenoviruses are able to induce different diseases from moderate respiratory disorders to fatal outcomes in patients with immunodeficiencies. The authors present the results of a trial of the antiviral activity of the new drug Ingavirin [2-(imidazole-4-yl-ethanamide) pentandioic-1,5 acid] against human adenovirus type 5 on an animal model. Ingavirin is shown to decrease an adenoviral infectious titer in the liver and lung of neonatal Syrian hamsters (by approximately 1 log10 TCID50 as compared to the control) and to reduce the sizes of liver inflammation foci by 2-fold. Furthermore, it also decreases the count of virus-infected cells detectable by morphological analysis. Hepatocytes from Ingavirin-treated animals appear intact unlike strongly vacuolized cells from the animals given placebo. The findings make it possible to regard Ingavirin as a promising agent of the combination therapy of human adenovirus disease.

[Effect of antiviral drugs with various mechanisms of action on morphogenesis of infection caused by extremely pathogenic influenza virus strains in animals].

The effect of meglumine salt of acridonoacetic acid (cycloferon) on the in vivo morphogenesis of influenza infection caused by viruses of different origin (avian, swine and human) and variable susceptibility to antivirals (rimantadine and oseltamivir) has been studied. The administration of cycloferon results in stimulation of the immune response, restriction of the foci of post-influenza pneumonia, and normalization of the structure of respiratory zones independently of the susceptibility or resistance of infectious virus to the drugs. Among virions formed in the lungs of cycloferon-treated mice, prevalence of irregular-shaped virions with defects of surface glycoproteins was observed. The data obtained suggest that cycloferon is a drug with the complex mechanism of activity.

[Protective activity of Ingavirin in experimental lethal influenza due to pandemic influenza virus A (H1N1)v in albino mice].

Despite obvious success in the vaccine development and chemotherapy of influenza, it remains a poorly controlled infection leading to emergence of new pandemic variants of the virus with high morbidity and mortality. We investigated the protective activity of Ingavirin against the lethal influenza A (H1N1) 2009 virus infection on albino mice. Oral use of Ingavirin resulted in sharp decreasing of the mortality (index of protection up to 57%), slight decreasing of the infectious titer of the virus in the lungs (up to 40-fold), normalizing of the body weight dynamics and the lung tissue structure vs. the placebo-treated control. The degree of the bronchial epithelium damage was also strongly decreased. The results allow to consider Ingavirin as an effective antiviral against the current pandemic influenza virus.