Potential for Protein Kinase Pharmacological Regulation in Flaviviridae Infections.

Potential for Protein Kinase Pharmacological Regulation in Flaviviridae Infections.
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DOI:
10.3390/ijms21249524
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发表时间:
2020-12-15
影响因子:
5.6
通讯作者:
Saiz JC
Saiz JC
中科院分区:
生物学2区
文献类型:
--
作者:
Blázquez AB;Saiz JC

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蛋白激酶(PK)是催化末端磷酸基团从ATP转移到蛋白质受体(主要是丝氨酸、苏氨酸和酪氨酸残基)的酶。PK催化的磷酸化对于调节影响关键细胞过程(如生长、分化和代谢)的细胞信号传导途径至关重要。PK代表了针对包括病毒感染在内的广泛疾病的药物的有吸引力的靶标。两种不同的方法正在应用于寻找抗病毒药物:针对病毒靶点的化合物(直接作用的抗病毒药物,DAA),或针对病毒生命周期所必需的细胞组分的化合物(宿主导向的抗病毒药物,HDAs)。DAA的主要缺点之一是耐药病毒的快速出现。相比之下,HDA对耐药性发展具有更高的屏障。这项工作回顾了使用的化学物质,靶向细胞PKs作为HDAs对病毒的黄病毒科(黄病毒和Hepacivirus),从而成为潜在的有价值的治疗目标,在控制这些病原体。
Protein kinases (PKs) are enzymes that catalyze the transfer of the terminal phosphate group from ATP to a protein acceptor, mainly to serine, threonine, and tyrosine residues. PK catalyzed phosphorylation is critical to the regulation of cellular signaling pathways that affect crucial cell processes, such as growth, differentiation, and metabolism. PKs represent attractive targets for drugs against a wide spectrum of diseases, including viral infections. Two different approaches are being applied in the search for antivirals: compounds directed against viral targets (direct-acting antivirals, DAAs), or against cellular components essential for the viral life cycle (host-directed antivirals, HDAs). One of the main drawbacks of DAAs is the rapid emergence of drug-resistant viruses. In contrast, HDAs present a higher barrier to resistance development. This work reviews the use of chemicals that target cellular PKs as HDAs against virus of the Flaviviridae family (Flavivirus and Hepacivirus), thus being potentially valuable therapeutic targets in the control of these pathogens.
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