A series of novel 4-substituted sulfonamidobenzoic acid derivatives was synthesized as the structural evolution of 4-(4-(1,3-dioxoisoindolin-2-yl)phenylsulfonamido)benzoic acid, which is the known inhibitor of the enterovirus life cycle. Antiviral properties of prepared compounds were evaluated in vitro using phenotypic screening and viral yield reduction assay. Their capsid binding properties were verified in thermostability assay. We identified two new hit-compounds (4 and 7a) with high activity against the coxsackievirus B3 (Nancy, CVB3) strain with potencies (IC50 values of 4.29 and 4.22 μM, respectively) which are slightly superior to the reference compound 2a (IC50 5.54 μM). Both hits changed the heat inactivation of CVB3 in vitro to higher temperatures, suggesting that they are capsid binders, as 2a is. The results obtained can serve as a basis for further development of the lead compounds for novel drug design to combat enterovirus infection.
A series of 2,4-disubstituted pyrrolo[2,1-f][1,2,4]triazines containing both aryl and thienyl substituents were synthesized by exploiting the 1,3-cycloaddition reaction of N(1)-ethyl-1,2,4-triazinium tetrafluoroborates with dimethyl acetylenedicarboxylate. The antiviral activity of the synthesized compounds against influenza virus strain A/Puerto Rico/8/34 (H1N1) was studied in experiments on Madin-Darby canine kidney (MDCK) cell culture. Among the pyrrolo[2,1-f][1,2,4]triazine derivatives, compounds with low toxicity and high antiviral activity were identified. Dimethyl 4-(4-methoxyphenyl)-7-methyl-2-p-tolylpyrrolo[2,1-f][1,2,4]triazine-5,6-dicarboxylate was found to demonstrate the best antiviral activity (IC50 4 µg/mL and selectivity index 188). Based on the results of in vitro tests and molecular docking studies performed, a plausible mechanism of action for these compounds was suggested to involve inhibition of neuraminidase.
15 June 2015 in Epidemiology and Infectious Diseases
Interferon-gamma (IFN-y) is a pleiotropic lymphokine that have multiple effects on the growth and differentiation of various types of cells associated with innate immunity. IFN-y induces differentiation ofmyeloid cells, stimulates the expression of major histocompatibility complex (MHC) class II and class I antigens, it is a potent activator of macrophages which destroy antigenic molecules penetrating the cell. IFN-y is widely used for the treatment of infectious diseases, cancer, autoimmune and allergic diseases. Studies conducted in Research Institute ofInfluenza indicate that drugs IFN-y can be successfully usedfor prevention of influenza and acute respiratory infection (ARI) during the rise of incidence, as well as for the treatment - the first few days/ hours of the onset. The concomitant use of drugs as IFN-a and IFN-y on influenza and ARI can greatly improve the prophylactic and therapeutic efficacy.
15 October 2015 in Epidemiology and Infectious Diseases
By force of hormonal and physiological changes occurring in the body throughout pregnancy, in the case of the flu, pregnant women are at greater risk of developing complications. In this regard, the study of clinical and pathogenetic features of influenza in pregnant women deserves special attention. So, on the basis of epidemiological data over the past few decades, WHO experts have included pregnant women in groups at risk of severe (complicated) course of the flu. The flu for a pregnant female is a dangerous infection, representing a real threat to the health of the expectant mother and her child. The clinical picture of influenza in pregnant women can vary significantly, and severe complications combine with the development of a pathology of pregnancy, which ultimately exacerbates the condition as well an expectant mother as the fetus. For the study both of the character of the clinical course of influenza in pregnant women and the mechanism of the immunosuppressive state FGBU "Influenza Research Institute" performed a simple multi-center comparative study on the base of the infectious-disease units of the GBOU "NGMU" and the Medical University "KrasGMU named after. prof. V.F. Voyno-Yasenetsky" of the Ministry of Health of the Russian Federation. The obtained results allowed to reveal some clinical and immunological features of the course of influenza in pregnant women: at the peak of the disease there was noted a significant inhibition of induced production of IFN-γ.