摘要
背景:流感病毒在季节性流行期间会引起儿童和老年人的严重上呼吸道疾病。来自人畜共患病水库的流感病毒也会引起大流行,所有年龄段的人都会严重死亡。虽然疫苗接种是预防季节性流行病最有效的方法之一,但季节性疫苗的效力各不相同,在老年人群中可能无效,并且不能提供对新菌株的保护。小分子疗法是我们控制流感病毒流行和大流行以及改善老年人和免疫受损人群疾病的抗病毒策略的关键部分。 目的:综述目前流行性感冒病毒的抗病毒治疗策略、现有药物的抗病毒机制以及目前正在开发的新疗法。 方法:对已发表的科学文献进行系统的评价和综合,为流感病毒的治疗策略提供理论依据。 结果:当前IAV株对神经氨酸酶抑制剂产生耐药性,对M2离子通道抑制剂几乎完全耐药,治疗和化学预防用亚治疗剂量加重。新的策略包括针对宿主成分的新疗法和联合疗法,这显示了在最大限度减少病毒抵抗的同时对抗流感病毒疾病的潜力。 结论:抗病毒药物是控制流感病毒疾病负担的关键,但其有效性受到人类滥用和流感病毒绕过抗病毒屏障的能力的限制。为了缓解流感病毒的公共卫生困境,必须选择新的治疗方法,因为它们不仅能够阻止流感病毒疾病,而且能够发展抗病毒能力。
关键词: 流感病毒,抗病毒耐药性,小分子治疗,抗流感药物,抗病毒耐药性,抗病毒药物。
Current Medicinal Chemistry
Title:Influenza Virus: Small Molecule Therapeutics and Mechanisms of Antiviral Resistance
Volume: 25 Issue: 38
关键词: 流感病毒,抗病毒耐药性,小分子治疗,抗流感药物,抗病毒耐药性,抗病毒药物。
摘要: Background: Influenza viruses cause severe upper respiratory illness in children and the elderly during seasonal epidemics. Influenza viruses from zoonotic reservoirs can also cause pandemics with significant loss of life in all age groups. Although vaccination is one of the most effective methods to protect against seasonal epidemics, seasonal vaccines vary in efficacy, can be ineffective in the elderly population, and do not provide protection against novel strains. Small molecule therapeutics are a critical part of our antiviral strategies to control influenza virus epidemics and pandemics as well as to ameliorate disease in elderly and immunocompromised individuals.
Objective: This review aims to summarize the existing antiviral strategies for combating influenza viruses, the mechanisms of antiviral resistance for available drugs, and novel therapeutics currently in development.
Methods: We systematically evaluated and synthesized the published scientific literature for mechanistic detail into therapeutic strategies against influenza viruses.
Results: Current IAV strains have developed resistance to neuraminidase inhibitors and nearly complete resistance to M2 ion channel inhibitors, exacerbated by sub-therapeutic dosing used for treatment and chemoprophylaxis. New tactics include novel therapeutics targeting host components and combination therapy, which show potential for fighting influenza virus disease while minimizing viral resistance.
Conclusion: Antiviral drugs are crucial for controlling influenza virus disease burden, but their efficacy is limited by human misuse and the capacity of influenza viruses to circumvent antiviral barriers. To relieve the public health hardship of influenza virus, emerging therapies must be selected for their capacity to impede not only influenza virus disease, but also the development of antiviral resistance.
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Cite this article as:
Influenza Virus: Small Molecule Therapeutics and Mechanisms of Antiviral Resistance, Current Medicinal Chemistry 2018; 25 (38) . https://dx.doi.org/10.2174/0929867324666170920165926
DOI https://dx.doi.org/10.2174/0929867324666170920165926 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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