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

Wang, K.; Chen, W.; Zhou, Y.-S.; Lian, J.-Q.; Zhang, Z.; Du, P.; Gong, L.; Zhang, Y.; Cui, H.-Y.; Geng, J.-J.; Wang, B.; Sun, X.-X.; Wang, C.-F.; Yang, X.; Lin, P.; Deng, Y.-Q.; Wei, D.; Yang, X.-M.; Zhu, Y.-M.; Zhang, K.; Zheng, Z.-H.; Miao, J.-L.; Guo, T.; Shi, Y.; Zhang, J.; Fu, L.; Wang, Q.-Y.; Bian, H.; Zhu, P.; Chen, Z.-N.

doi:10.1101/2020.03.14.988345

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bioRxiv · 10.1101/2020.03.14.988345

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

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Abstract

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 g/mL and IC50 of 15.16 g/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85x10-7M. 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.

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Wang, K., Chen, W., Zhou, Y.-S., Lian, J.-Q., Zhang, Z., Du, P., Gong, L., Zhang, Y., Cui, H.-Y., Geng, J.-J., Wang, B., Sun, X.-X., Wang, C.-F., Yang, X., Lin, P., Deng, Y.-Q., Wei, D., Yang, X.-M., Zhu, Y.-M., Zhang, K., Zheng, Z.-H., Miao, J.-L., Guo, T., Shi, Y., Zhang, J., Fu, L., Wang, Q.-Y., Bian, H., Zhu, P., Chen, Z.-N.. 2020-03-14. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. https://doi.org/10.1101/2020.03.14.988345

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