SARS-CoV-2 manipulates the SR-B1-mediated HDL uptake pathway for its entry

Wei, Congwen; Wan, Luming; Yan, Qiulin; Wang, Xiaolin; Zhang, Jun; Zhang, Yanhong; Sun, Jin; Yang, Xiaopan; Gong, Jing; Fan, Chen; Yang, Xiaoli; Wang, Yufei; Wang, Xuejun; Li, Jianmin; Yang, Huan; Li, Huilong; Zhang, Zhe; Wang, Rong; Du, Peng; Zong, Yulong; Yin, Feng; Zhang, Wanchuan; Peng, Yumeng; Lin, Haotian; Zhang, Rui; Chen, Wei; Gao, Qi; Cao, Yuan; Zhong, Hui

The recently emerged pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global COVID-19 pandemic. Binding of the viral spike protein (SARS-2-S) to cell surface receptor angiotensin-converting enzyme 2 (ACE2) mediates host cell infection. In the present study, we demonstrate that in addition to ACE2, the S1 subunit of SARS-2-S binds to HDL and that SARS-CoV-2 hijacks the SR-B1-mediated HDL uptake pathway to facilitate its entry. SR-B1 facilitates SARS-CoV-2 entry into permissive cells by augmenting virus attachment. MAb (monoclonal antibody)-mediated blocking of SARS-2-S-HDL binding and SR-B1 antagonists strongly inhibit HDL-enhanced SARS-CoV-2 infection. Notably, SR-B1 is co-expressed with ACE2 in human pulmonary and extrapulmonary tissues. These findings revealed a novel mechanism for SARS-CoV-2 entry and could provide a new target to treat SARS-CoV-2 infection.