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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:p>\n                    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and\/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (K\n                    <jats:sub>D<\/jats:sub>\n                    ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor\/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2317026121","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T15:00:36Z","timestamp":1708959636000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":47,"title":["Human transferrin receptor can mediate SARS-CoV-2 infection"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1998-9763","authenticated-orcid":false,"given":"Zhiyi","family":"Liao","sequence":"first","affiliation":[{"name":"Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic &amp; Genetic Analysis of Model Animals (Primate Facility), and Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming..."},{"name":"Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoming","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic &amp; Genetic Analysis of Model Animals (Primate Facility), and Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming..."},{"name":"Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic &amp; 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