Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, Viale F. Stagno D'Alcontres, Messina, 98166, Italy.
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, Milano, 20126, Italy.
Curr Med Chem. 2024;31(18):2507-2549. doi: 10.2174/0929867331666230907093501.
In recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention of chemists is continuously focused on the synthesis of new antiviral drugs able to interact with the different molecular targets involved in the virus replication cycle. To date, different classes of influenza viruses inhibitors able to target neuraminidase enzyme, hemagglutinin protein, Matrix-2 (M2) protein ion channel, nucleoprotein or RNAdependent RNA polymerase have been synthesized using several synthetic strategies comprising the chemical modification of currently used drugs. The best results, in terms of inhibitory activity, are in the nanomolar range and have been obtained from the chemical modification of clinically used drugs such as Peramivir, Zanamivir, Oseltamir, Rimantadine, as well as sialylated molecules, and hydroxypyridinone derivatives. The aim of this review is to report, covering the period 2016-2022, the most recent routes related to the synthesis of effective influenza virus inhibitors.
近几十年来,世界已经积累了应对新兴呼吸道病毒引起的大流行病的危险影响的经验。特别是,流感的年度流行会导致严重的疾病和死亡。即使传统的流感疫苗是预防病毒感染最有效的工具,但它们在严重慢性疾病和免疫功能低下的患者中并不完全有效,并且已经出现了新的小分子来预防和控制流感病毒。因此,化学家们一直将注意力集中在合成能够与病毒复制周期中涉及的不同分子靶标相互作用的新型抗病毒药物上。迄今为止,已经使用了几种合成策略,包括对当前使用的药物进行化学修饰,合成了能够靶向神经氨酸酶、血凝素蛋白、基质-2 (M2) 蛋白离子通道、核蛋白或 RNA 依赖性 RNA 聚合酶的不同类别的流感病毒抑制剂。在抑制活性方面,最好的结果是在纳摩尔范围内,并且已经从对目前临床使用的药物如 Peramivir、Zanamivir、Oseltamir、Rimantadine 以及唾液酸化分子和羟吡啶酮衍生物的化学修饰中获得。本文综述了 2016 年至 2022 年期间,与合成有效流感病毒抑制剂相关的最新途径。