Rhinoviruses (RVs) cause the common cold and are associated with exacerbations of chronic inflammatory respiratory diseases, especially asthma and chronic obstructive pulmonary disease (COPD). We have assessed the antiviral drugs Anaferon for Children (AC) and Ergoferon (containing AC as one of the active pharmaceutical ingredients) in in vitro and in vivo experimental models, in order to evaluate their anti-rhinoviral and immunomodulatory potential. HeLa cells were pretreated with AC, and levels of the interferon-stimulated gene (ISG), 2'-5'-oligoadenylate synthetase 1 (OAS1-A) and viral replication were analyzed. In a mouse model of RV-induced exacerbation of allergic airway inflammation we administered Ergoferon and analyzed its effect on type I (IFN-β), type II (IFN-γ) and type III (IFN-λ) IFNs induction, cell counts in bronchoalveolar lavage (BAL), cytokine (interleukin (IL)-4; IL-6) and chemokine (CXCL10/IP-10; CXCL1/KC) levels. It was shown that AC increased OAS1-А production and significantly decreased viral replication in vitro. Increased IFNs expression together with reduced neutrophils/lymphocytes recruitment and correlated IL-4/IL-6 declination was demonstrated for Ergoferon in vivo. However, there was no effect on examined chemokines. We conclude that AC and Ergoferon possess effects against RV infection and may have potential as novel therapies against RV-induced exacerbations of asthma.

Доклиническое изучение эффективности нового иммунотропного препарата при лечении сальмонеллезной инфекции

Background: Nitric oxide (NO) as a vaso- and cardio-protective agent could reduce vasomotor dysfunction in different cardiovascular diseases. One of the current therapeutics targeted at NO availability in the vascular wall are highly diluted antibodies to endothelial NO-synthase (eNOS). This drug has previously shown its endothelium-protective effect and effectiveness in reducing hypertension. Current study was dedicated to evaluate the direct impact of highly diluted antibodies to eNOS on the vessel constriction and dilation ex vivo. Methods: For that purpose, we used thoracic aortas dissected from spontaneously hypertensive (SHR) rats. Endothelium-dependent relaxation in the presence of highly diluted antibodies to eNOS (1 mL) was examined after phenylephrine-induced pre-constriction of the aorta rings in response to gradually increased acetylcholine concentration (1 nM to 10 µM). Results: Highly diluted antibodies to eNOS enhanced acetylcholine-induced relaxation in a statistically significant manner. Moreover, it was demonstrated that observed effect was similar to perindopril, a well-known angiotensin-converting-enzyme inhibitor, which works through relaxing and widening blood vessels. Conclusions: Our findings indicate that highly diluted antibodies to eNOS restored impaired endothelium function, as demonstrated by increased relaxation of SHR rats aorta rings. The revealed results suggest beneficial effect of highly diluted antibodies to eNOS to ameliorate hypertension and related diseases.

Роль молекул MHC I и II в антибактериальном иммунитете и лечении бактериальных инфекций

Due to the new coronavirus infection pandemic, the global scientific community has been forced to change the direction of the most research, focusing on vaccine development as well as the search for new antiviral drugs to treat COVID-19. The choice of experimental models, timeframe and approaches for evaluating drugs and vaccines under development is crucial for the development of effective measures to prevent and control this disease.The purpose of this review was to summarize the relevant data concerning the susceptibility of laboratory animals to SARS-CoV-2. This paper describes the most virus-susceptible animal species that can be used to reproduce coronavirus infection, stressing the main advantages and disadvantages of each of them.According to the latest data, small rodents (Rodentia) and non-human primates (Strepsirrhini) are commonly used in the scientific community to model coronavirus infection. The viral load in the upper and lower parts of the respiratory system, clinical symptoms of infection (weight loss, body temperature and general health status), pathomorphological picture in target organs and the production of antibodies after infection are considered to the main markers of pathology. Despite the vast amount of data, none of the described models of SARS-CoV-2 infection may be considered a gold standard, since they do not reproduce all spectrum of morphological and pathogenetic mechanisms of infection, and do not fully reflect the clinical picture observed in patients in human population.Based on the analyzed literature data, we suppose that Syrian hamster (Mesocricetus auratus) and mice (Muridae) expressing the angiotensin converting enzyme receptor 2 (ACE2) are the most suitable animal species for their use in experiments with SARS-CoV-2 infection. The development of neutralizing antibodies makes it possible to evaluate the efficacy of vaccines, while the course and severity of symptoms infection makes the use of mice and hamsters especially popular for screening pharmacological substances with antiviral mechanism of action, when their administration can prevent or slow the disease progression.