HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry

  • Nat Metab. 2020 Dec;2(12):1391-1400. doi: 10.1038/s42255-020-00324-0.
Congwen Wei   #  1 ,  Luming Wan   #  1 ,  Qiulin Yan   #  1  2 ,  Xiaolin Wang   #  1 ,  Jun Zhang   #  1 ,  Xiaopan Yang   #  1 ,  Yanhong Zhang  1 ,  Chen Fan  3 ,  Dongyu Li  1 ,  Yongqiang Deng  4 ,  Jin Sun  1 ,  Jing Gong  1  2 ,  Xiaoli Yang  5 ,  Yufei Wang  5 ,  Xuejun Wang  6 ,  Jianmin Li  1 ,  Huan Yang  1 ,  Huilong Li  1 ,  Zhe Zhang  1 ,  Rong Wang  1 ,  Peng Du  1 ,  Yulong Zong  7 ,  Feng Yin  7 ,  Wanchuan Zhang  8 ,  Nan Wang  8 ,  Yumeng Peng  1 ,  Haotian Lin  1 ,  Jiangyue Feng  1 ,  Chengfeng Qin  4 ,  Wei Chen  1 ,  Qi Gao  9 ,  Rui Zhang  10 ,  Yuan Cao  11 ,  Hui Zhong  12
Affiliations
  • 1. Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing, China.
  • 2. Institute of Physical Science and Information Technology, Anhui University, Hefei, China.
  • 3. Department of Basic Medical Sciences, The 960th Hospital of PLA, Jinan, China.
  • 4. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China.
  • 5. Department of Clinical Laboratory, the Third Medical Centre, Chinese PLA General Hospital, Beijing, China.
  • 6. Beijing Institute of Radiation Medicine, AMMS, Beijing, China.
  • 7. Department of Laboratory Medicine, Taian City Central Hospital Branch, Taian, China.
  • 8. Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
  • 9. Beijing Hotgen Biotech Co., Ltd., Beijing, China.
  • 10. Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China. [email protected].
  • 11. Department of Basic Medical Sciences, The 960th Hospital of PLA, Jinan, China. [email protected].
  • 12. Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing, China. [email protected].
  • # Contributed equally.
PMID: 33244168 DOI: 10.1038/s42255-020-00324-0
Abstract

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to Cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 Infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 Infection.

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