AUTHOR=Ren Yujie , Wang An , Fang Yuan , Shu Ting , Wu Di , Wang Chong , Huang Muhan , Min Juan , Jin Liang , Zhou Wei , Qiu Yang , Zhou Xi 

TITLE=SARS-CoV-2 Membrane Glycoprotein M Triggers Apoptosis With the Assistance of Nucleocapsid Protein N in Cells

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.706252

DOI=10.3389/fcimb.2021.706252

ISSN=2235-2988

ABSTRACT=The pandemic of COVID-19 caused by SARS-CoV-2 has become a global crisis. However, the understanding about how individual SARS-CoV-2-encoded proteins contribute to viral pathogenicity is still limited. Herein, we uncovered that SARS-CoV-2-encoded membrane glycoprotein M can induce caspase-dependent apoptosis via interacting with PDK1 and inhibiting the activation of PDK1-PKB/Akt signaling. Our further investigation revealed that SARS-CoV-2-encoded nucleocapsid protein N can specifically enhance the M-induced apoptosis via interacting with both M and PDK1, which strengthens M-mediated attenuation of PDK1-PKB/Akt interaction. Moreover, when the M-N interaction was disrupted via certain rationally designed peptide, the PDK1-PKB/Akt signalling was restored and the enhancing activity of N on the M-triggered apoptosis was abolished. Overall, our findings uncovered a novel mechanism by which SARS-CoV-2-encoded M triggers apoptosis with the assistance of N, which extends our knowledge about the two key proteins of SARS-CoV-2 and sheds light onto the pathogenicity of this life-threatening virus.