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SARS-CoV-2 3CL^pro的Cys44会影响其催化活性

Ilaria Iacobucci¹, Irene Cipollone², Flora Cozzolino¹

¹Department of Chemical Sciences, University of Naples "Federico II", Via Cintia, 21, 80126 Napoli, Italy; CEINGE Advanced Biotechnologies s.c.a r.l. "Franco Salvatore", Via Gaetano Salvatore 486, 80131 Napoli, Italy.

International journal of biological macromolecules

|January 9, 2025

概括

氨酸通过对氨酸残留物 (包括催化Cys145和功能Cys44) 进行共价结合来抑制SARS-CoV-2 3C样蛋白酶 (3CL^pro). 这揭示了素.

科学领域:

病毒学病毒学
药物发现药物发现药物发现
生物化学生物化学

背景情况:

严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 依赖其3C样蛋白酶 (3CL^pro) 进行病毒复制.
3CL^pro是一种氨酸蛋白酶,对于将病毒多蛋白分裂为功能蛋白质至关重要,使其成为抗病毒药物开发的关键目标.

研究的目的:

研究一种已知的c-Jun N-终端激酶抑制剂素对SARS-CoV-2 3CL^pro的抑制作用.
阐明抑制的机制,并确定素与3CL^pro的相互作用中的关键残留物.

主要方法:

质谱和晶体分析以确定3CL^pro上的素的结合位.
生成Cys44Ala突变蛋白酶,以评估Cys44.4的作用.
在基,酶和差异扫描度测试中评估蛋白质酶的稳定性和活性.

主要成果:

素与3CL^pro中的氨酸残留物结合,主要准催化Cys145并修改Cys44.
Cys44Ala突变显著降低了3CL^pro的稳定性和酶活性,突出显示了Cys44在维持蛋白酶活性构造中的重要性.
与野生型3CL^pro相比,差异扫描度证实Cys44Ala突变体的热稳定性降低.

结论:

素通过与关键的氨酸残留物相互作用,作为SARS-CoV-2 3CL^pro的多目标抑制剂.
在维护3CL^pro的结构完整性和功能方面,Cys44起着至关重要的作用.
这些发现支持开发针对COVID-19治疗3CL^pro的特定残留物的新型抗病毒疗法.

关键词:

药物重新定位是药物重新定位.氨酸是氨酸中的一种.在Sars-CoV-2 3Cl (((pro) 中.

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