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针对(重新)出现的虫媒病毒疾病登革热和寨卡病毒的甲基转移酶(MTase)抑制剂开发的最新进展。

Recent advances in the development of methyltransferase (MTase) inhibitors against (re)emerging arboviruses diseases dengue and Zika.

作者信息

Delgado-Maldonado Timoteo, Moreno-Herrera Antonio, Pujadas Gerard, Vázquez-Jiménez Lenci K, González-González Alonzo, Rivera Gildardo

机构信息

Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710, Reynosa, Mexico.

Departament de Bioquímica i Biotecnologia, Research group in Cheminformatics & Nutrition, Campus de Sescelades, Universitat Rovira i Virgili, 43007, Tarragona, Catalonia, Spain.

出版信息

Eur J Med Chem. 2023 Apr 5;252:115290. doi: 10.1016/j.ejmech.2023.115290. Epub 2023 Mar 20.

Abstract

Emerging and/or re-emerging viral diseases such as dengue and Zika are a worldwide concern. Therefore, new antiviral therapeutics are necessary. In this sense, a non-structural protein with methyltransferase (MTase) activity is an attractive drug target because it plays a crucial role in dengue and Zika virus replication. Different drug strategies such as virtual screening, molecular docking, and molecular dynamics have identified new inhibitors that bind on the MTase active site. Therefore, in this review, we analyze MTase inhibitors, including S-adenosyl-L-methionine (SAM), S-adenosyl-l-homocysteine (SAH) and guanosine-5'-triphosphate (GTP) analogs, nitrogen-containing heterocycles (pyrimidine, adenosine, and pyridine), urea derivatives, and natural products. Advances in the design of MTase inhibitors could lead to the optimization of a possible single or broad-spectrum antiviral drug against dengue and Zika virus.

摘要

登革热和寨卡等新出现和/或重新出现的病毒性疾病是全球关注的问题。因此,新的抗病毒疗法是必要的。从这个意义上说,具有甲基转移酶(MTase)活性的非结构蛋白是一个有吸引力的药物靶点,因为它在登革热和寨卡病毒复制中起关键作用。虚拟筛选、分子对接和分子动力学等不同的药物策略已经鉴定出结合在MTase活性位点上的新抑制剂。因此,在本综述中,我们分析了MTase抑制剂,包括S-腺苷-L-甲硫氨酸(SAM)、S-腺苷-L-高半胱氨酸(SAH)和鸟苷-5'-三磷酸(GTP)类似物、含氮杂环(嘧啶、腺苷和吡啶)、尿素衍生物和天然产物。MTase抑制剂设计方面的进展可能会导致针对登革热和寨卡病毒的单一或广谱抗病毒药物的优化。

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