Новые стратегии терапии респираторных инфекций (English) - статья в международном журнале

Abstract Respiratory viral infections are a leading cause of disease and economic burden. Severity of these illnesses is not the only source of challenges for patients. Each acute respiratory viral infection episode can markedly trigger inflammatory status in human body: from acute inflammation during the first days of the disease proceeding to systemic chronic inflammation later in weeks and even months. In this article, we review the viral sensing pathways and organizing principles that govern the immune response to infection. Then, we describe a lysosomotropic activity of novel drug candidates as a game-changing strategy for respiratory viral infections treatment, reflecting a novel approach in host response-directed therapy. Finally, we discuss unique aspects of the biology and pathogenesis of infections with respiratory syncytial virus, rhinovirus, influenza, and etc, drawing on insights from completed physiologically based pharmacokinetic modelling for lysosomotropic characteristics of new generation of imidazole-based compounds - XC221, XC8 and XC55. Introduction Intermittent increases in physiological reparative inflammation are necessary for survival during physical injury and infection. However, recent research has shown that certain social, environmental, and lifestyle factors are triggers for specific immune-mediated reaction called systemic chronic inflammation (SCI). This type of inflammation means an existence of smoldering inflammatory lesions through the organ systems which can lead to several diseases, such as cardiovascular disease, сhronic pulmonary diseases, non-alcoholic fatty liver disease, inflammatory bowel disease, diabetes mellitus, vaginal yeast infection and bacterial vaginosis, autoimmune and neurodegenerative disorders. These diseases caused by initial inappropriate inflammatory overactivation to infection or trauma are the leading causes of disability and mortality around the world. Over the past two decades, one of the most important medical discoveries has been the involvement of the immune system and inflammatory processes in a wide range of mental and physical health problems. This highlights the significance of chronic inflammatory diseases, which have been recognized as the leading cause of death worldwide, marking so called “inflammation-targeted approach” as a priority to keep better quality of health and life in adulthood [Furman et al., 2017; Netea et al., 2017; Slavich et al., 2015; Bennet et al., 2018]. Inflammation-related diseases such as ischemic heart disease, stroke, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease (NAFLD), and autoimmune and neurodegenerative conditions account for more than 50% of all deaths. On the other hand, chronic cough, bacterial vaginosis, and candidiasis do not lead to fatal cases but decrease daily activity, quality of life, and happiness level, as well as impoverish a significant part of economically active population all over the world. It is now evident that the risk of developing chronic inflammation can be traced back to previous episodes of acute diseases with unresolved inflammation activity, and its effects persist throughout the lifespan, affecting adulthood health and the risk of mortality [Miller et al., 2011; Fleming et al., 2018; Renz et al., 2017]. ... полный текст статьи - в прикрепленном файле