Influenza Virus: Small Molecule Therapeutics and Mechanisms of Antiviral Resistance.
Influenza Virus: Small Molecule Therapeutics and Mechanisms of Antiviral Resistance.
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流感病毒：抗病毒抗性的小分子疗法和机制。
DOI：
10.2174/0929867324666170920165926
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发表时间：
2018
影响因子：
4.1
通讯作者：
Manicassamy B
中科院分区：
文献类型：
--
作者：
Han J;Perez J;Schafer A;Cheng H;Peet N;Rong L;Manicassamy B
流感病毒在季节性流行期间会导致儿童和老年人严重的上呼吸道疾病。来自人畜共患宿主的流感病毒也可能引起大流行，导致所有年龄段的人大量死亡。尽管疫苗接种是预防季节性流行病的最有效方法之一，但季节性疫苗的功效各不相同，对老年人群可能无效，并且不能提供针对新毒株的保护。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功能低下个体疾病的抗病毒策略的重要组成部分。本综述旨在总结现有的对抗流感病毒的抗病毒策略、现有药物的抗病毒耐药机制以及目前正在开发的新疗法。我们系统地评估和综合了已发表的科学文献，以了解流感病毒的治疗策略的机制细节。目前的 IAV 菌株已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，用于治疗和化学预防的亚治疗剂量加剧了这种耐药性。新策略包括针对宿主成分的新型疗法和联合疗法，这些疗法显示出对抗流感病毒疾病的潜力，同时最大限度地减少病毒耐药性。抗病毒药物对于控制流感病毒疾病负担至关重要，但其功效受到人类滥用和流感病毒规避抗病毒屏障的能力的限制。为了缓解流感病毒造成的公共卫生困难，必须选择新兴疗法，因为它们不仅能够阻止流感病毒疾病，而且能够阻止抗病毒耐药性的发展。
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. 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. We systematically evaluated and synthesized the published scientific literature for mechanistic detail into therapeutic strategies against influenza viruses. 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. 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.