HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry.
Nat Metab
; 2(12): 1391-1400, 2020 12.
Article
in English
| MEDLINE | ID: covidwho-947555
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Scavenger Receptors, Class B
/
Virus Internalization
/
Host-Pathogen Interactions
/
SARS-CoV-2
/
COVID-19
/
Lipoproteins, HDL
Limits:
Humans
Language:
English
Journal:
Nat Metab
Year:
2020
Document Type:
Article
Affiliation country:
S42255-020-00324-0
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