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抗人腺病毒药物的开发及其在叙利亚仓鼠模型中的进展。

Drug development against human adenoviruses and its advancement by Syrian hamster models.

机构信息

Saint Louis University School of Medicine, Department of Molecular Microbiology and Immunology, 1100 S. Grand Boulevard, St. Louis, MO, USA.

出版信息

FEMS Microbiol Rev. 2019 Jul 1;43(4):380-388. doi: 10.1093/femsre/fuz008.

Abstract

The symptoms of human adenovirus infections are generally mild and self-limiting. However, these infections have been gaining importance in recent years because of a growing number of immunocompromised patients. Solid organ and hematopoietic stem cell transplant patients are subjected to severe immunosuppressive regimes and cannot efficaciously eliminate virus infections. In these patients, adenovirus infections can develop into deadly multi-organ disseminated disease. Presently, in the absence of approved therapies, physicians rely on drugs developed for other purposes to treat adenovirus infections. As there is a need for anti-adenoviral therapies, researchers have been developing new agents and repurposing existing ones to treat adenovirus infections. There are several small molecule drugs that are being tested for their efficacy against human adenoviruses; some of these have reached clinical trials, while others are still in the preclinical phase. Besides these compounds, research on immunotherapy against adenoviral infection has made significant progress, promising another modality for treatment. The availability of an animal model confirmed the activity of some drugs already in clinical use while proving that others are inactive. This led to the identification of several lead compounds that await further development. In the present article, we review the current status of anti-adenoviral therapies and their advancement by in vivo studies in the Syrian hamster model.

摘要

人类腺病毒感染的症状通常较轻且具有自限性。然而,由于越来越多的免疫功能低下患者,这些感染近年来变得越来越重要。实体器官和造血干细胞移植患者接受严重的免疫抑制治疗,无法有效地消除病毒感染。在这些患者中,腺病毒感染可能发展为致命的多器官播散性疾病。目前,由于缺乏批准的治疗方法,医生依赖于为其他目的开发的药物来治疗腺病毒感染。由于需要抗腺病毒治疗,研究人员一直在开发新的药物并重新利用现有的药物来治疗腺病毒感染。有几种小分子药物正在被测试其对人类腺病毒的疗效;其中一些已进入临床试验阶段,而另一些仍处于临床前阶段。除了这些化合物,针对腺病毒感染的免疫疗法研究也取得了重大进展,为治疗提供了另一种方法。动物模型的可用性证实了一些已在临床使用的药物的活性,同时证明了其他药物的无效性。这导致了一些先导化合物的鉴定,这些化合物有待进一步开发。在本文中,我们回顾了抗腺病毒治疗的现状及其在叙利亚仓鼠模型中的体内研究进展。

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