In addition to investigating the virology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovering the host–virus dependencies are essential to identify and design effective antiviral therapy strategy. Here, we report that the SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) and provide evidence indicating that prevention of ACE2 SUMOylation can block SARS-CoV-2 infection. E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. TOLLIP deficiency results in the stabilization of ACE2 and elevated SARS-CoV-2 infection. In conclusion, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination as a potential way to combat SARS-CoV-2 infection.
【초록키워드】 SARS-CoV-2, antiviral therapy, ACE2, coronavirus, SARS-COV-2 infection, lysine, receptor, Degradation, Evidence, deficiency, acute respiratory syndrome, enzyme, entry receptor, selective, conjugation, effective, conjugate, identify, subsequent, addition, elevated, autophagic, PIAS4, SENP3, SUMO3, the SARS-CoV-2, TOLLIP, 【제목키워드】 ACE2, SARS-COV-2 infection, autophagy, suppression, selective, PROTECT,