Transferrin receptor is another receptor for SARS-CoV-2 entry

Tang, X.; Yang, M.; Duan, Z.; Liao, Z.; Liu, L.; Cheng, R.; Fang, M.; Wang, G.; Liu, H.; Xu, J.; Kamau, P. M.; Zhang, Z.; Yang, L.; Zhao, X.; Peng, X.; Lai, R.

doi:10.1101/2020.10.23.350348

bioRxiv · 10.1101/2020.10.23.350348

Transferrin receptor is another receptor for SARS-CoV-2 entry

Tang, X.·Yang, M.·Duan, Z.·Liao, Z.·Liu, L.·Cheng, R.·Fang, M.·Wang, G.·Liu, H.·Xu, J.·Kamau, P. M.·Zhang, Z.·Yang, L.·Zhao, X.·Peng, X.·Lai, R.

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Abstract

Angiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ~16.6 nM) shows promising anti-viral effects in mouse model. Collectively, this report indicates that TfR is another receptor for SARS-CoV-2 entry and a promising anti-COVID-19 target.

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Tang, X., Yang, M., Duan, Z., Liao, Z., Liu, L., Cheng, R., Fang, M., Wang, G., Liu, H., Xu, J., Kamau, P. M., Zhang, Z., Yang, L., Zhao, X., Peng, X., Lai, R.. 2020-10-23. Transferrin receptor is another receptor for SARS-CoV-2 entry. https://doi.org/10.1101/2020.10.23.350348

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