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一种针对膜蛋白的小分子SARS-CoV-2抑制剂

Ellen Van Damme¹, Pravien Abeywickrema², Yanting Yin²

¹Global Public Health R&D, Janssen Pharmaceutica, Beerse, Belgium.

|March 27, 2025

概括

一种新的小分子抑制剂,JNJ-9676,向betacoronaviruses的保护膜 (M) 蛋白. 这种化合物在临床前模型中显示出强大的抗病毒活性和有效性,为抗击冠状病毒大流行提供了有希望的策略.

科学领域:

病毒学
药物发现
结构生物学

背景情况:

膜 (M) 蛋白对于β冠状病毒的组合至关重要,并且是一种保存的病毒成分.
开发针对M蛋白的抑制剂是对抗冠状病毒的可行策略.

研究的目的:

识别和描述针对冠状病毒M蛋白的新型小分子抑制剂.
评估已识别的抑制剂对SARS-CoV-2和相关病毒的抗病毒活性和有效性.

主要方法:

对各种β冠状病毒菌株进行了体外抗病毒检测.
使用冷电子显微镜 (cryo-EM) 确定结合部位和作用机制.
临床前的疗效在叙利亚黄金仓鼠模型中进行了评估 (暴露前和暴露后).

主要成果:

JNJ-9676在实验室中显示出对SARS-CoV-2,SARS-CoV和动物性沙贝科病毒的纳米分子抗病毒活性.
低温检测显示JNJ-9676与M蛋白二次体结合,稳定了改变的形状并防止病毒的释放.
在仓鼠模型中观察到肺部病毒载量和传染性病毒的显著减少,其组织病理正常化.

结论:

新冠病毒M蛋白是抗病毒开发的有希望的目标.
JNJ-9676是一种强大的M蛋白抑制剂,在临床前模型中已证明有效,代表了冠状病毒流行病的潜在临床候选者.

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