Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon^® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon^® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

Introduction: In this research, we evaluate the effect of intravenously administrated solubilized ubiquinol on 4-week monocrotalin-induced pulmonary hypertension (PH) in rats. Materials and methods: To reproduce the model, some male Wistar rats were subcutaneously injected with alcohol solution of monocrotaline60 mg/kg and the rest – with alcohol solution (Control). Those with monocrotaline (MCT) were divided into 3 groups. They underwent intravenous administration of 1% ubiquinol solution 30 mg/kg (MCT-Ubiquinol), the vehicle (MCT-Vehicle) and saline (MCT-saline) three times on days 7, 14 and 21, depending on the group. The hemodynamic parameters were measured in anesthetized rats on day 29. Right ventricle hypertrophy, pulmonary arteries reactivity and expression of miRNA-21 and miRNA-34a were estimated after euthanasia. Results and discussion: All MCT-groups demonstrated an increase in right ventricle systolic pressure and hypertrophy in comparison with the control group. An increase in lung weight was shown in MCT-Vehicle and MCT-Saline; however, the MCT-Ubiquinol indicators did not differ from those of the Control. There was an increased vasodilatation response to acetylcholine at concentrations of 1*10-6M and 1*10-5M in MCT-Ubiquinol in contrast to the other two MCT-groups. A significantly lower level of expression of miRNA-34a was observed in MCT-Ubiquinol. Conclusion: Our findings suggest that a triple ubiquinol injection influences pulmonary changes and endothelium-depended vasodilatation, which contributes to pulmonary vascular tone and reactivity. A decrease in miRNA-34a expression in MCT-Ubiquinol group demonstrates the ubiquinol anti-inflammatory properties.

Введение. Сужение легочных сосудов является одним из факторов патогенеза гипоксической формы легочной гипертонии (ГЛГ). Степень развития заболевания зависит от степени гипоксического воздействия и пола. Цель – изучение влияния степени гипоксии и пола животного на реакции изолированных легочных артерий на вазоактивные факторы. Материалы и методы. Эксперименты проводили на гонадоэктомированных самцах (СЦ) и самках (СК) крыс стока Wistar. В эксперимент вступало по 4 группы животных. Одна группа СЦ и СК содержалась в условиях вивария (21 %О₂ ). Для моделирования ГЛГ остальных крыс в течение по 10 ч в сутки подвергали действию гипобарической гипоксии (ХПГГ) при содержании кислорода во вдыхаемом воздухе 13 % (пД. О₂ 103,7 мм рт. ст.), или 10 % (пД. О₂ 78,2 мм рт. ст.), или 8 % (пД. О₂ 63,5 мм рт. ст.) в сравнении с его содержанием при 21 % (пД О₂ 159 мм рт. ст). Затем выделяли легочный сосуд 3-го порядка, который перфузировали с постоянным расходом сосудосуживающими и сосудорасширяющими агентами. О реакции судили по изменению перфузионного давления. Результаты. Изучение реакций изолированных сосудов показало, что у СК с ГЛГ 10 % О₂ суживающая реакция на серотонин была больше, чем у СЦ. У нормотензивных СЦ расширительный ответ на эндотелий-независимый расширительный фактор нитропруссид натрия (НП) была меньше, чем у СК. Воздействие гипоксии у СЦ приводило к увеличению реактивности к НП. Заключение. Увеличенная реактивность легочных сосудов СК к серотонину может быть фактором патогенеза ГЛГ, в отличие от СЦ. Увеличение реакции к NO-донору у СЦ при действии гипоксии может быть использовано для фармакологической коррекции ГЛГ.

INTRODUCTION . Developing high-dose interferon-based medicinal products (MPs) is particularly relevant for effective causal treatment of acute respiratory viral infections, influenza, and COVID-19 coronavirus infection. Inhalation drops both act directly on mucous membranes and stimulate powerful immune response and increased safety profile. In 2021, a new medicinal product, interferon alpha-2b-based inhalation drops, was developed to treat influenza and acute respiratory viral infections of various aetiologies. AIM . This study aimed to assess preclinical efficacy, subchronic toxicity, and toxicokinetics of a new MP based on interferon alpha-2b and administered by inhalation. MATERIALS AND METHODS . The new MP is based on human recombinant interferon alpha-2b. Its efficacy was studied on female BALB/c mice. The animals inhaled 3 mL of the investigational product for 10 minutes twice a day for 8 days. Animals were infected with A(H1N1)pdm2009 on Day 2 of inhalation. The dynamics of body weight and mortality, as well as influenza titre in the murine lung tissues, were evaluated 4 days after infection. MP toxicity was studied on white non-linear rats of both sexes. MP was administered using an inhaler once a day for 7 weeks at doses exceeding human therapeutic dose by 5.3 and 53 times. Pathomorphological and histopathological examination was performed on Days 29 and 43 of administration. Haematological and biochemical blood parameters, heart rate, and behavioural functions were measured prior to administration, 4 weeks into administration, and 2 weeks after the last administration. Toxicokinetics was studied on satellite groups of male rats; administration scheme was similar to toxicity studies. RESULTS . Experiments showed that inhalation of investigational product at 923,000 IU/kg/day twice a day for 8 days inhibited A(H1N1)pdm2009 replication in the murine lungs, significantly reduced animal mortality and weight loss, and increased animal life expectancy 1.35–1.5-fold. The study doses showed no pronounced toxic, local irritant or systemic effect. CONCLUSIONS . The inhalation investigational product has shown its efficacy and safety in preclinical studies on rodents.