PDF(Sci-hub)
Abstract：
Introduction: Despite the current interest caused by SARS-Cov-2, influenza continues to be one of the most serious health concerns, with an estimated 1 billion cases across the globe, including 3-5 million severe cases and 290,000-650,000 deaths worldwide. Areas covered: This manuscript reviews the efforts made in the development of small molecules for the treatment of influenza virus, primarily focused on patent applications in the last 5 years. Attention is paid to compounds targeting key functional viral proteins, such as the M2 channel, neuraminidase, and hemagglutinin, highlighting the evolution toward new ligands and scaffolds motivated by the emergence of resistant strains. Finally, the discovery of compounds against novel viral targets, such as the RNA-dependent RNA polymerase, is discussed. Expert opinion: The therapeutic potential of antiviral agents is limited by the increasing presence of resistant strains. This should encourage research on novel strategies for therapeutic intervention. In this context, the discovery of arbidol and JNJ7918 against hemagglutinin, and current efforts on RNA-dependent RNA polymerase have disclosed novel opportunities for therapeutic treatment. Studies should attempt to expand the therapeutic arsenal of anti-flu agents, often in combined therapies, to prevent future health challenges caused by influenza virus. Abbreviations: AlphaLISA: amplified luminescent proximity homogeneous assay; HA: hemagglutinin; NA: neuraminidase; RBD: receptor binding domain; RdRp: RNA-dependent RNA polymerase; SA: sialic Acid; TBHQ: tert-butyl hydroquinone; TEVC: two-electrode voltage clamp.
摘要：
简介:尽管目前SARS-Cov-2引起了人们的兴趣，但流感仍然是最严重的健康问题之一，估计全球有10亿例，包括全球300万至500万例严重病例和29万至65万例死亡。涵盖的领域：本手稿回顾了在开发用于治疗流感病毒的小分子方面所做的努力，过去5年主要集中在专利申请上。注意靶向关键功能病毒蛋白的化合物，例如M2通道，神经氨酸酶，和血凝素，突出了由抗性菌株的出现推动的向新配体和支架的进化。最后,针对新型病毒靶标的化合物的发现，例如依赖RNA的RNA聚合酶，正在讨论。专家意见：抗病毒药物的治疗潜力受到耐药菌株增加的限制。这应该鼓励研究治疗干预的新策略。在这种情况下，阿比多尔和JNJ7918抗血凝素的发现，和目前对RNA依赖性RNA聚合酶的努力已经揭示了治疗性治疗的新机会。研究应该试图扩大抗流感药物的治疗武器库，通常在联合疗法中，预防未来由流感病毒引起的健康挑战。缩写:AlphaLISA:扩增发光邻近同质测定;HA:血凝素;NA:神经氨酸酶;RBD:受体结合域;RdRp:RNA依赖性RNA聚合酶;SA:唾液酸;TBHQ:叔丁基氢醌;TEVC:双电极电压钳。
