Advances in the Development of Non-Structural Protein 1 (NsP1) Inhibitors for the Treatment of Chikungunya Virus Infection.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-01-01 DOI:10.2174/0113895575301735240607055839

Timoteo Delgado-Maldonado, Antonio Moreno-Herrera, Gildardo Rivera

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Abstract

Chikungunya is a re-emerging viral infection of worldwide concern, and new antiviral therapeutics are necessary to combat this disease. Inhibitors of the non-structural protein 1 (NsP1), which shows Methyltransferase (MTase) activity and plays a crucial in the Chikungunya virus (ChikV) replication, are exhibiting promising results. This review aimed to describe recent advances in the development of NsP1 inhibitors for the treatment of Chikungunya disease. High-throughput screening of novel ChikV NsP1 inhibitors has been widely performed for the identification of new molecule hits through fluorescence polarization, Western blotting, ELISA-based assay, and capillary electrophoresis assays. Additionally, cell-based assays confirmed that the inhibition of ChikV NsP1 abolishes viral replication. In summary, pyrimidine and pyrimidin-7(6H)-one derivatives, GTP and nucleoside analogs have been demonstrated to show inhibitory activity and are considered promising scaffolds that provide useful knowledge for the research and development of new NsP1 inhibitors as potential treatment of Chikungunya re-emerging disease.

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用于治疗基孔肯雅病毒感染的非结构蛋白 1 (NsP1) 抑制剂的开发进展。

基孔肯雅病毒是一种重新出现的病毒感染，受到全世界的关注，因此需要新的抗病毒疗法来防治这种疾病。非结构蛋白 1（NsP1）具有甲基转移酶（MTase）活性，在基孔肯雅病毒（ChikV）复制过程中起着关键作用，其抑制剂正显示出良好的效果。本综述旨在介绍开发用于治疗奇昆古尼亚病毒疾病的 NsP1 抑制剂的最新进展。新型 ChikV NsP1 抑制剂的高通量筛选已广泛开展，通过荧光偏振、Western 印迹、基于酶联免疫吸附试验和毛细管电泳试验来鉴定新的分子。此外，基于细胞的试验证实，抑制 ChikV NsP1 可抑制病毒复制。总之，嘧啶和嘧啶-7(6H)-酮衍生物、GTP 和核苷类似物已被证明具有抑制活性，被认为是有前景的支架，为研究和开发新的 NsP1 抑制剂提供了有用的知识，有望治疗基孔肯雅再流行病。.

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