Department of Microbiology, The University of Chicago, Chicago, Illinois 60637, United States.
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
Curr Med Chem. 2018;25(38):5115-5127. doi: 10.2174/0929867324666170920165926.
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.
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。来自动物宿主的流感病毒也可能引发大流行，导致所有年龄段的人群大量死亡。尽管疫苗接种是预防季节性流行的最有效方法之一，但季节性疫苗的效果各不相同，在老年人群体中可能无效，并且不能预防新型菌株。小分子治疗药物是我们控制流感病毒流行和大流行以及改善老年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抗病毒策略，以对抗流感病毒，以及现有药物的抗病毒耐药机制和当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，以了解针对流感病毒的治疗策略的机制细节。
目前的 IAV 株已经对神经氨酸酶抑制剂产生了耐药性，并且对 M2 离子通道抑制剂几乎完全耐药，治疗和化学预防中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治疗方法和联合治疗，这显示出在最小化病毒耐药性的同时对抗流感病毒疾病的潜力。
抗病毒药物对于控制流感病毒疾病负担至关重要，但由于人类的误用以及流感病毒规避抗病毒屏障的能力，其疗效受到限制。为了减轻流感病毒对公共卫生的影响，新兴疗法必须因其不仅能抑制流感病毒疾病，而且还能抑制抗病毒耐药性的发展的能力而被选择。
