Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) as a binding receptor to enter cells via clathrin-mediated endocytosis (CME). However, receptors involved in other steps of SARS-CoV-2 infection remain largely unknown. Here, we found that metabotropic glutamate receptor subtype 2 (mGluR2) is an internalization factor for SARS-CoV-2. Our results show that mGluR2 directly interacts with the SARS-CoV-2 spike protein and that knockdown of mGluR2 decreases internalization of SARS-CoV-2 but not cell binding. Further, mGluR2 is uncovered to cooperate with ACE2 to facilitate SARS-CoV-2 internalization through CME and mGluR2 knockout in mice abolished SARS-CoV-2 infection in the nasal turbinates and significantly reduced viral infection in the lungs. Notably, mGluR2 is also important for SARS-CoV spike protein- and Middle East respiratory syndrome coronavirus spike protein-mediated internalization. Thus, our study identifies a novel internalization factor used by SARS-CoV-2 and opens a new door for antiviral development against coronavirus infection.
【저자키워드】 Molecular biology, Mechanisms of disease, 【초록키워드】 SARS-CoV-2, viral infection, Coronavirus infection, ACE2, coronavirus, Antiviral, SARS-COV-2 infection, angiotensin-converting enzyme 2, Spike protein, mice, Lungs, receptor, Glutamate, binding, Clathrin-mediated endocytosis, Middle East, nasal turbinate, acute respiratory syndrome, SARS-CoV spike protein, knockdown, respiratory syndrome coronavirus, Cell, decrease, identify, significantly, involved, reduced, facilitate, interact, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, receptor, Glutamate, infect cell,