Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, Spain.
Int J Mol Sci. 2020 Dec 15;21(24):9524. doi: 10.3390/ijms21249524.
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 family ( and ), thus being potentially valuable therapeutic targets in the control of these pathogens.
蛋白激酶(PKs)是一类酶,能够催化 ATP 末端磷酸基团向蛋白质受体的转移,主要是丝氨酸、苏氨酸和酪氨酸残基。PK 催化的磷酸化对细胞信号通路的调节至关重要,这些信号通路影响着关键的细胞过程,如生长、分化和代谢。PKs 是针对广泛疾病(包括病毒感染)的药物的有吸引力的靶标。在寻找抗病毒药物时,采用了两种不同的方法:针对病毒靶标的化合物(直接作用抗病毒药物,DAAs)或针对病毒生命周期所必需的细胞成分的化合物(宿主定向抗病毒药物,HDAs)。DAAs 的主要缺点之一是耐药病毒的迅速出现。相比之下,HDAs 的耐药性发展的障碍更高。这项工作综述了靶向细胞 PKs 的化学物质作为抗病毒药物( 和 )的用途,因此它们是控制这些病原体的潜在有价值的治疗靶标。