Jinliang Wang # , Guan Yang # , Xinxin Wang # , Zhiyuan Wen , Lei Shuai , Jie Luo, Chong Wang, Ziruo Sun, Renqiang Liu, Jinying Ge, Xijun He, Ronghong Hua, Xijun Wang, Xiao Yang, Weiye Chen, Gongxun Zhong, Zhigao Bu

Cell Discov.2021 Dec 14;7(1):119.doi: 10.1038/s41421-021-00357-z.

Abstract

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.