Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Methods Mol Biol. 2022;2556:321-353. doi: 10.1007/978-1-0716-2635-1_21.
Depending on the strain, influenza A virus causes animal, zoonotic, pandemic, or seasonal influenza with varying degrees of severity. Two surface glycoprotein spikes, hemagglutinin (HA) and neuraminidase (NA), are the most important influenza A virus antigens. NA plays an important role in the propagation of influenza virus by removing terminal sialic acid from sialyl decoy receptors and thereby facilitating the release of viruses from traps such as in mucus and on infected cells. Some NA inhibitors have become widely used drugs for treatment of influenza. However, attempts to develop effective and safe NA inhibitors that can be used for treatment of anti-NA drugs-resistant influenza viruses have continued. In this chapter, we describe the following updates on influenza A NA inhibitor development: (i) N-acetylneuraminic acid (Neu5Ac)-based derivatives, (ii) covalent NA inhibitors, (iii) sulfo-sialic acid analogs, (iv) N-acetyl-6-sulfo-β-D-glucosaminide-based inhibitors, (v) inhibitors targeting the 150-loop of group 1 NAs, (vi) conjugation inhibitors, (vii) acylhydrazone derivatives, (viii) monoclonal antibodies, (ix) PVP-I, and (x) natural products. Finally, we provide future perspectives on the next-generation anti-NA drugs.
根据病毒株的不同，甲型流感病毒会导致动物流感、人畜共患流感、大流行流感或季节性流感，其严重程度各有不同。两种表面糖蛋白刺突，血凝素（HA）和神经氨酸酶（NA），是最重要的甲型流感病毒抗原。NA 通过从唾液酸诱饵受体上移除末端唾液酸，从而促进病毒从黏液和受感染细胞等陷阱中释放，在流感病毒的传播中发挥着重要作用。一些 NA 抑制剂已成为治疗流感的广泛使用的药物。然而，人们一直致力于开发有效且安全的 NA 抑制剂，以用于治疗抗 NA 药物耐药性流感病毒。在本章中，我们描述了甲型流感 NA 抑制剂开发的以下最新进展：（i）基于 N-乙酰神经氨酸（Neu5Ac）的衍生物，（ii）共价 NA 抑制剂，（iii）磺酸唾液酸类似物，（iv）N-乙酰-6-磺酸-β-D-葡糖胺基抑制剂，（v）靶向 1 组 NAs 的 150 环的抑制剂，（vi）缀合抑制剂，（vii）酰腙衍生物，（viii）单克隆抗体，（ix）PVP-I 和（x）天然产物。最后，我们对下一代抗 NA 药物的未来前景进行了展望。
