SARS-CoV-2 Membrane protein regulates the function of Spike by inhibiting its plasma membrane localization and enzymatic activity of Furin.
Microbiol Res
; 282: 127659, 2024 May.
Article
de En
| MEDLINE
| ID: mdl-38430890
ABSTRACT
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-2â¯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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Furine
/
COVID-19
Limites:
Humans
Langue:
En
Journal:
Microbiol Res
Sujet du journal:
MICROBIOLOGIA
/
SAUDE AMBIENTAL
Année:
2024
Type de document:
Article