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Transferrin receptor is another receptor for SARS-CoV-2 entry
Xiaopeng Tang; Mengli Yang; Zilei Duan; Zhiyi Liao; Lei Liu; Ruomei Cheng; Mingqian Fang; Gan Wang; Hongqi Liu; Jingwen Xu; Peter M Kamau; Zhiye Zhang; Lian Yang; Xudong Zhao; Xiaozhong Peng; Ren Lai.
Affiliation
  • Xiaopeng Tang; Kunming Institute of Zoology, Chinese Academy of Sciences
  • Mengli Yang; Institute of Medical Biology, Chinese Academy of Medical Sciences
  • Zilei Duan; Kunming Institute of Zoology, Chinese Academy of Sciences
  • Zhiyi Liao; Kunming Institute of Zoology, Chinese Academy of Sciences
  • Lei Liu; West China Hospital, Sichuan University
  • Ruomei Cheng; Kunming Institute of Zoology, Chinese Academy of Sciences
  • Mingqian Fang; Kunming Institute of Zoology, Chinese Academy of Sciences
  • Gan Wang; Kunming Institute of Zoology, Chinese Academy of Sciences
  • Hongqi Liu; Institute of Medical Biology, Chinese Academy of Medical Sciences
  • Jingwen Xu; Institute of Medical Biology, Chinese Academy of Medical Sciences
  • Peter M Kamau; Kunming Institute of Zoology, Chinese Academy of Sciences
  • Zhiye Zhang; Kunming Institute of Zoology, Chinese Academy of Sciences
  • Lian Yang; Kunming Institute of Botany, Chinese Academy of Sciences
  • Xudong Zhao; West China Hospital, Sichuan University
  • Xiaozhong Peng; Institute of Medical Biology, Chinese Academy of Medical Sciences
  • Ren Lai; Kunming Institute of Zoology, Chinese Academy of Sciences
Preprint in English | bioRxiv | ID: ppbiorxiv-350348
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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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint
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