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. Epub 2020 Nov 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / metabolism*
  • COVID-19 / virology*
  • Cell Line
  • Cholesterol / metabolism
  • Disease Susceptibility
  • Host-Pathogen Interactions*
  • Humans
  • Lipoproteins, HDL / metabolism*
  • Protein Binding
  • Receptors, Virus
  • SARS-CoV-2 / physiology*
  • Scavenger Receptors, Class B / metabolism*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Viral Tropism
  • Virus Attachment
  • Virus Internalization*


  • Lipoproteins, HDL
  • Receptors, Virus
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Spike Glycoprotein, Coronavirus
  • Cholesterol