生物
毛皮
酶
膜
膜蛋白
功能(生物学)
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
细胞生物学
生物化学
2019年冠状病毒病(COVID-19)
病毒学
医学
疾病
病理
传染病(医学专业)
作者
Qi Xiang,Jie Wang,Yuzheng Zhou,Linhao Li,Miao Tian,Guobao Li,Zheng Zhang,Yang Fu
标识
DOI:10.1016/j.micres.2024.127659
摘要
The presence of a multibasic cleavage site in the Spike protein of SARS-CoV-2 makes it prone to be cleaved by Furin at the S1/S2 junction (aa. 685-686), which enhances the usage of TMPRSS2 to promote cell-cell fusion to form syncytia. Syncytia may contribute to pathology by facilitating viral dissemination, cytopathicity, immune evasion, and inflammation. However, the role of other SARS-CoV-2 encoding viral proteins in syncytia formation remains largely unknown. Here, we report that SARS-CoV-2 M protein effectively inhibits syncytia formation triggered by Spike or its variants (Alpha, Delta, Omicron, etc.) and prevents Spike cleavage into S1 and S2 based on a screen assay of 20 viral proteins. Mechanistically, M protein interacts with Furin and inhibits its enzymatic activity, preventing the cleavage of Spike. In addition, M interacts with Spike independent of its cytoplasmic tail, retaining it within the cytoplasm and reducing cell membrane localization. Our findings offer new insights into M protein's role in regulating Spike's function and underscore the importance of functional interplay among viral proteins, highlighting potential avenues for SARS-CoV-2 therapy development.
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