Ближневосточный респираторный синдром (БВРС) – это острое воспалительное заболевание дыхательной системы, возбудителем которого является коронавирус БВРС-КоВ. Летальность при БВРС составляет 34.5%. В связи с высокой летальностью, отсутствием терапевтических и профилактических средств и сохраняющейся угрозой распространения БВРС за пределы эндемичных районов разработка вакцинного препарата является актуальной задачей, а вакцинопрофилактика против БВРС позволит ограничить распространение БВРС и снизить летальность. Нами была разработана комбинированная векторная вакцина для профилактики БВРС на основе рекомбинантных аденовирусов человека 26 и 5 серотипа. Проведенные исследования иммуногенности показали, что вакцинация животных (мыши и приматы) позволяет сформировать мощный гуморальный иммунный ответ, который сохраняется на протяжении не менее 6 месяцев. Исследования клеточного иммунного ответа у мышей после вакцинации показали формирование выраженного специфического CD4 + и CD8 + ответа. По результатам исследования протективности вакцины на модели трансгенных мышей, несущих ген рецептора DPP4 человека, было показано, что вакцинация обеспечивает защиту 100% животных от летальной инфекции, вызванной вирусом БВРС-КоВ (MERS-CoV EMC/2012, 100 ЛД 50 /мышь). Проведенные исследования безопасности и переносимости разработанной вакцины у грызунов, кроликов и приматов показали хорошую переносимость вакцины у животных и не выявили противопоказаний для проведения клинических исследований.

Studies have been carried out to study the effectiveness of the high-molecular inducer of interferon Larifan® in relation to the experimental form of severe acute respiratory syndrome in Syrian hamsters. It is shown that Lariphan® is effective when applied in a preventive scheme, and the scheme of emergency prevention. The coefficient of therapeutic action for virological, hematological and biochemical parameters was 57.5 and 65.0%, respectively (ð<0.05 and ð<0.01).

Коронавирус ближневосточного респираторного синдрома (БВРС-КоВ) был идентифицирован в 2012 году во время первых вспышек ближневосточного респираторного синдрома (БВРС). БВРС-КоВ вызывает острую инфекцию нижних дыхательных путей у человека, летальность при которой составляет ~35%. Зарегистрированные средства профилактической и терапевтической защиты против БВРС в насто ящее время отсутствуют. Гликопротеин S БВРС-КоВ играет важнейшую роль в интернализации вируса. Белок S является иммунодоминантным антигеном и основной мишенью для нейтрализующих антител. Нами проведено сравнение иммуногенности пяти различных форм гликопротеина S БВРС-КоВ: полнораз мерного гликопротеина S, полноразмерного гликопротеина S с трансмембранным доменом гликопротеина G вируса VSV (S-G), рецепторсвязывающего домена RBD гликопротеина S, мембраносвязанного RBD (слитого с трансмембранным доменом гликопротеина G вируса VSV, RBD-G) и RBD, слитого с Fc-фрагментом IgG1 человека (RBD-Fc). Для доставки использовали рекомбинантные векторы на основе аденовируса человека серотипа 5 (rAd5). Вакцинация мышей всеми разработанными векторами rAd5 позволила сформировать сбалансированный Th1/Th2-ответ. Наиболее мощный антительный ответ развивался при иммунизации животных мембраносвязанным RBD (rAd5-RBD-G). Формирование нейтрализующих антител у всех вак цинированных животных наблюдалось только при иммунизации мембранными формами гликопротеина (rAd5-S, rAd5-S-G и rAd5-RBD-G). Наиболее выраженный клеточный ответ развивался при иммунизации животных полноразмерным S (rAd5-S). Проведенные исследования позволяют предположить, что среди всех изученных форм гликопротеина S наиболее перспективными для включения в вакцину против БВРС являются полноразмерный S и мембранная форма RBD (RBD-G).

The claimed invention relates to the development of a novel substance, 4-((2-hydroxyethoxy)methyl)-5-methyl-2-methylmercapto-1,2,4-triazolo[1,5-a]pyrimidine-7(4H)-one, having the formula (I) and being intended for the treatment of West Nile Virus in humans and animals. A method for producing 4-((2-hydroxyethoxy)methyl)-5-methyl-2-methylmercapto-1,2,4-triazolo[1,5-a]pyrimidine-7(4H)-one consists in the deacetylation of 4-((2-acetoxyethoxy)methyl)-5-methyl-2-methylmercapto-1,2,4-triazolo[1,5-a]pyrimidine-7(4H)-one (II) under the action of a solution of an alkali metal methylate in aliphatic monovalent alcohol, wherein 4-((2-acetoxyethoxy)methyl)-5-methyl-2-methylmercapto-1,2,4-triazolo[1,5-a]pyrimidine-7(4H)-one (II) is produced by reacting 5-methyl-2-methylmercapto-1,2,4-triazolo[1,5-a]pyrimidine-7(4H)-one (III) with (2-acetoxyethoxy)methylacetate (IV) in the presence of a siliconizing agent, for example N,O-bis(trimethylsilyl)acetamide (BSA) or hexamethyldisilylamine (HMDS) and trimethylsilyl trifluoromethylsulfonate (TMSOTf) in an aprotic solvent. 4-((2-hydroxyethoxy)methyl)-5-methyl-2-methylmercapto-1,2,4-triazolo[1,5-a]pyrimidine-7(4H)-one can be used to treat West Nile Virus (WNV).

The efficacy of Triazavirin against the tick-borne encephalitis virus was estimated in the sensitive cell culture vs. the active drug Ribavirin. In a concentration of 128 mcg/ml Triazavirin was shown active in inhibition of the tick-borne encephalitis virus reproduction (strain Sofiin) by accumulation in the SKEV cell culture.

The peculiarities of the spread of vaccine-like viruses first revealed more than 50 years ago in the area of the South America was discussed. These viruses cause infective episodes among milk cattle and caretaking personnel. Cancellation of the smallpox vaccination in 1980 resulted in a decrease in the community immunity and increased the risks of human infection. This circumstance makes it necessary to activate monitoring of the properties of the vaccine-like viruses, the circle of hosts and possible changes in the pathogenicity for humans.

FIELD: chemistry. SUBSTANCE: invention relates to organic chemistry and specifically 4-((2-hydroxyethoxy)methyl)-5-methyl-2-methylmercapto-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one of formula (I) . The invention also relates to a method of producing and using said compound to treat West Nile fever. EFFECT: obtaining a novel compound with useful biological activity. 3 cl, 2 tbl, 4 ex

AIMStudy of immunogenicity and protective efficacy of a novel inactivated vaccine with chitosan against influenza A/H1N1/2009.MATERIALS AND METHODSInfluenza virus A/California/7/2009 (H1N1) strain was used in the study. Mice were immunized twice (21 day interval) with experimental samples of inactivated influenza vaccine: No. 1--without the addition of chitosan, No. 2--with addition of chitosan. The blood was obtained 21 days after the first and 10 days after the second immunization with the vaccines and was treated with RDE. Antibody levels were evaluated in HI reaction.RESULTSHI reaction method showed that antibody titers induced after immunization of vaccine No. 2 were higher than those induced after immunization with vaccine No. 1. Evaluation of protective efficacy of the vaccines against an experimental form of influenza infection in mice showed that after immunization with vaccine that does not contain chitosan the level of virus accumulation does not differ from the control statistically significantly (p < or = 0.05), at the same time the level of virus accumulation in the lungs of infected animals immunized with chitosan containing vaccine significantly (significantly with 95% probability) decreased by an average 3.01g when compared with control.CONCLUSIONComparative analysis of immunogenicity and protective efficacy of experimental samples of inactivated influenza vaccine against influenza A/H 1N1/2009 showed that the vaccine with the addition of chitosan stimulates the formation of a higher immune response and promotes a more significant suppression of influenza A infectious agent reproduction in the lung target-organ.

The study of the toxicity of triazavirin, a new antiinfluenza agent, showed that the maximum concentration of the drug, inducing no microscopically visible changes in the structure of the monolayer and the cells of the MDCK and SKEV cell cultures, was 128 and 100 mcg/ml respectively. The maximum drug dose for single intraperitoneal administration inducing no signs of acute intoxication in albino mice weighing 10-12 g was 1000 mg/kg. In investigation of the chronic toxicity it was shown that oral administration of the drug (by 0.05 ml) to the albino mice in a dose of 200 mg/kg (maximum possible concentration by the solubility) daily for 10 days was well tolerated by the laboratory animals. The maximum tolerable dose of triazavirin for the albino mice was > or = 200 mg/kg.

Analysis of the efficacy of Grippferon vs. the reference drugs Realdiron and Reaferon-EC against the influenza virus A(H1N1)/2009 in susceptible static cell cultures showed that in the concentrations tested it was efficient in inhibition of the virus cytopathic activity and generation of specific hemagglutinin.

The role of reamberin, a succinate-containing infusion preparation in correlation of pulmonary metabolic and respiratory disturbances in patients with obstetric puerperal sepsis was estimated. The prospective randomized study enrolled 43 patients with puerperal obstetric sepsis complicated by polyorganic deficiency (SOFA 8-10). Nineteen patients of the 1st group and 24 patients of the 2nd group were additionally treated with reamberin in a dose of 800 ml/day for 8 days. The venous and arterial difference by glucose, lactate, pyruvate, diene conjugates, malondialdehyde and ceruloplasmin was investigated. The blood gases were determined with the Ciba Corning 45 apparatus. Lower metabolic activity of the lungs with prevalence of the glucose anaerobic metabolism and lower activity of the intrapulmonary antioxidant protection were observed in the patients with obstetric sepsis. The use of reamberin in the complex therapy of obstetric sepsis promoted maintenance of the initial balance and anaeroibic and aerobic pulmonary metabolism, thus providing shorter terms of the decompensation and recovery of the lungs respiratory function.

Foreign experience with empirical management of severe acute respiratory syndrome (SARS) due to coronavirus, genotype IV is described. It is indicated that the data on the efficacy of ribavirin with respect to SARS in the patients are contradictory. The efficacy of two chemotherapeutics, i. e. lopinavir and ritonavir used in the SARS foci is confirmed. The drugs are at present applicable all over the world in retrovirus therapy of HIV infected subjects. The search for efficient Russian unspecific medicines for control of SARS is actual.

Efficacy of arbidol and ridostin in cupping postvaccinal complications due to variolation was studied by the clinico-virological, hematological and biochemical indices and it was shown that arbidol was efficient in cupping development of dermal complications, lowered the severity of the postvaccinal reaction and stimulated the cellular and humoral immune response. Ridostin, a high molecular interferon inductor, was highly efficient in cupping all the forms of the postvaccinal complications, including the neurological and cutaneous ones.