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英加韦林(6-[2-(1H-咪唑-4-基)乙氨基]-5-氧代己酸)在体内实验中对人类呼吸道病毒的活性。

Activity of Ingavirin (6-[2-(1H-Imidazol-4-yl)ethylamino]-5-oxo-hexanoic Acid) Against Human Respiratory Viruses in in Vivo Experiments.

作者信息

Zarubaev Vladimir V, Garshinina Angelica V, Kalinina Nelly A, Shtro Anna A, Belyaevskaya Svetlana V, Slita Alexander V, Nebolsin Vladimir E, Kiselev Oleg I

机构信息

Influenza Research Institute, 15/17 prof. Popova str., St. Petersburg 197376, Russia.

ValentaPharm, Ltd., 18 block 2, Gen. Dorokhova str., Moscow 119530, Russia.

出版信息

Pharmaceuticals (Basel). 2011 Nov 25;4(12):1518-1534. doi: 10.3390/ph4121518.

Abstract

Respiratory viral infections constitute the most frequent reason for medical consultations in the World. They can be associated with a wide range of clinical manifestations ranging from self-limited upper respiratory tract infections to more devastating conditions such as pneumonia. In particular, in serious cases influenza A leads to pneumonia, which is particularly fatal in patients with cardiopulmonary diseases, obesity, young children and the elderly. In the present study, we show a protective effect of the low-molecular weight compound Ingavirin (6-[2-(1H-imidazol-4-yl)ethylamino]-5-oxohexanoic acid) against influenza A (H1N1) virus, human parainfluenza virus and human adenovirus infections in animals. Mortality, weight loss, infectious titer of the virus in tissues and tissue morphology were monitored in the experimental groups of animals. The protective action of Ingavirin was observed as a reduction of infectious titer of the virus in the lung tissue, prolongation of the life of the infected animals, normalization of weight dynamics throughout the course of the disease, lowering of mortality of treated animals compared to a placebo control and normalization of tissue structure. In case of influenza virus infection, the protective activity of Ingavirin was similar to that of the reference compound Tamiflu. Based on the results obtained, Ingavirin should be considered as an important part of anti-viral prophylaxis and therapy.

摘要

呼吸道病毒感染是全球就医最常见的原因。它们可能与多种临床表现相关,从自限性上呼吸道感染到诸如肺炎等更具破坏性的疾病。特别是,严重情况下甲型流感会导致肺炎,这在患有心肺疾病、肥胖症的患者、幼儿和老年人中尤其致命。在本研究中,我们展示了低分子量化合物因加韦林(6-[2-(1H-咪唑-4-基)乙氨基]-5-氧代己酸)对甲型流感病毒(H1N1)、人副流感病毒和人腺病毒感染在动物模型中的保护作用。在动物实验组中监测了死亡率、体重减轻、组织中病毒的感染滴度以及组织形态。观察到因加韦林的保护作用表现为肺组织中病毒感染滴度降低、感染动物寿命延长、疾病全过程体重动态恢复正常、与安慰剂对照组相比治疗动物死亡率降低以及组织结构恢复正常。在流感病毒感染的情况下,因加韦林的保护活性与参考化合物达菲相似。基于所获得的结果,因加韦林应被视为抗病毒预防和治疗的重要组成部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1661/4060099/490e66c71d8f/pharmaceuticals-04-01518f1.jpg

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