Collaborative Innovation Center of New Drug Research and Safety Evaluation, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, 450001, China; Key Laboratory of "Runliang" Antiviral Medicines Research and Development, Institute of Drug Discovery & Development, Zhengzhou University, Zhengzhou, 450001, China.
College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, China.
Eur J Med Chem. 2022 Mar 15;232:114189. doi: 10.1016/j.ejmech.2022.114189. Epub 2022 Feb 15.
Influenza is a century-old disease that continues to baffle humans by its frequently changing nature, seasonal epidemics, and occasional pandemics. Approximately 9% of the world's population is infected by the influenza virus annually. The emergence of novel strains because of rapid mutations as well as interspecies disease contamination, limits the efficiency of strain-specific vaccines. Anti-influenza drugs such as neuraminidase inhibitors, M2 ion channel inhibitors, etc. have become the first line of defense in prophylaxis and early containment of the disease. But the growing drug resistance due to drug-induced selective pressure has also limited the efficacy of those drugs. Because we can't predict the next strain types, their virulence, or the severity of the next epidemic/pandemic caused by influenza virus, we ought to gear up for the development of novel anti-influenza drugs with a broad spectrum of reactivity against all strains and subtypes, better bioavailability, easier administrative pathways, and lesser adverse effects. Various new compounds with each having significantly different target molecules and pharmacologic activity have shown potential against influenza virus strains in laboratory situations as well as clinical trials. We should also consider combination therapy to boost the efficacy of existing drugs. This review is aiming to succinctly document the recent signs of progress regarding anti-influenza drugs both in the market and under investigation.
流感是一种具有百年历史的疾病,其频繁变化的性质、季节性流行和偶尔的大流行,使其一直困扰着人类。全球约有 9%的人口每年受到流感病毒的感染。由于快速突变和种间疾病污染,新型菌株的出现限制了针对特定菌株的疫苗的效率。抗流感药物,如神经氨酸酶抑制剂、M2 离子通道抑制剂等,已成为预防和早期控制疾病的第一道防线。但是,由于药物诱导的选择压力导致的耐药性不断增加,也限制了这些药物的疗效。由于我们无法预测下一个流感病毒株的类型、毒力或由其引发的下一次大流行/疫情的严重程度,我们应该加紧研发新型抗流感药物,这些药物应该对所有株和亚型具有广谱反应、更好的生物利用度、更简单的给药途径和更少的不良反应。各种具有显著不同靶分子和药理活性的新型化合物在实验室和临床试验中都显示出对流感病毒株的潜在疗效。我们还应该考虑联合治疗以提高现有药物的疗效。本综述旨在简明扼要地记录市场上和正在研究中的抗流感药物的最新进展。