SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Wang, Ke; Chen, Wei; Zhou, Yu-Sen; Lian, Jian-Qi; Zhang, Zheng; Du, Peng; Gong, Li; Zhang, Yang; Cui, Hong-Yong; Geng, Jie-Jie; Wang, Bin; Sun, Xiu-Xuan; Wang, Chun-Fu; Yang, Xu; Lin, Peng; Deng, Yong-Qiang; Wei, Ding; Yang, Xiang-Min; Zhu, Yu-Meng; Zhang, Kui; Zheng, Zhao-Hui; Miao, Jin-Lin; Guo, Ting; Shi, Ying; Zhang, Jun; Fu, Ling; Wang, Qing-Yi; Bian, Huijie; Zhu, Ping; Chen, Zhi-Nan

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 μg/mL and IC50 of 15.16 μg/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85×10−7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.