Szabat Marta, Lorent Dagny, Czapik Tomasz, Tomaszewska Maria, Kierzek Elzbieta, Kierzek Ryszard
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Pathogens. 2020 Nov 7;9(11):925. doi: 10.3390/pathogens9110925.
Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA-vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field.
由于流感对人类构成威胁,它是全球重要的研究课题。甲型流感病毒(IAV)引发季节性流行以及偶发但危险的大流行。病毒RNA基因组的快速抗原变化和重组导致疫苗接种和抗流感药物的效力降低。因此,有必要开发新的抗病毒药物和策略来限制流感传播。IAV是一种单链负义RNA病毒,其基因组(病毒RNA - vRNA)由八个片段组成。流感病毒粒子内的片段组装成病毒核糖核蛋白(vRNP)复合物,这些复合物是独立的转录 - 复制单元。流感病毒生命周期中的每一步都由RNA调控,并取决于其相互作用和动态变化。因此,病毒RNA可以成为设计新型疗法的合适靶点。在此,我们简要介绍了基于反义寡核苷酸(ASO)、小干扰RNA(siRNA)、微小RNA(miRNA)和催化核酸的抗流感策略实例。我们特别关注vRNA的结构 - 功能关系,并介绍了利用二级结构信息预测治疗靶点的优势以及该领域的潜在未来发展方向。