TY - JOUR
T1 - Photochemical Identification of Auxiliary Severe Acute Respiratory Syndrome Coronavirus 2 Host Entry Factors Using μmap
AU - Suzuki, Saori
AU - Geri, Jacob B.
AU - Knutson, Steve D.
AU - Bell-Temin, Harris
AU - Tamura, Tomokazu
AU - Fernández, David F.
AU - Lovett, Gabrielle H.
AU - Till, Nicholas A.
AU - Heller, Brigitte L.
AU - Guo, Jinchao
AU - Macmillan, David W.C.
AU - Ploss, Alexander
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/9/14
Y1 - 2022/9/14
N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of the COVID-19 pandemic, remains a global medical problem. Angiotensin-converting enzyme 2 (ACE2) was identified as the primary viral entry receptor, and transmembrane serine protease 2 primes the spike protein for membrane fusion. However, ACE2 expression is generally low and variable across tissues, suggesting that auxiliary receptors facilitate viral entry. Identifying these factors is critical for understanding SARS-Cov-2 pathophysiology and developing new countermeasures. However, profiling host-virus interactomes involves extensive genetic screening or complex computational predictions. Here, we leverage the photocatalytic proximity labeling platform μMap to rapidly profile the spike interactome in human cells and identify eight novel candidate receptors. We systemically validate their functionality in SARS-CoV-2 pseudoviral uptake assays with both Wuhan and Delta spike variants and show that dual expression of ACE2 with either neuropilin-2, ephrin receptor A7, solute carrier family 6 member 15, or myelin and lymphocyte protein 2 significantly enhances viral uptake. Collectively, our data show that SARS-CoV-2 synergistically engages several host factors for cell entry and establishes μMap as a powerful tool for rapidly interrogating host-virus interactomes.
AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of the COVID-19 pandemic, remains a global medical problem. Angiotensin-converting enzyme 2 (ACE2) was identified as the primary viral entry receptor, and transmembrane serine protease 2 primes the spike protein for membrane fusion. However, ACE2 expression is generally low and variable across tissues, suggesting that auxiliary receptors facilitate viral entry. Identifying these factors is critical for understanding SARS-Cov-2 pathophysiology and developing new countermeasures. However, profiling host-virus interactomes involves extensive genetic screening or complex computational predictions. Here, we leverage the photocatalytic proximity labeling platform μMap to rapidly profile the spike interactome in human cells and identify eight novel candidate receptors. We systemically validate their functionality in SARS-CoV-2 pseudoviral uptake assays with both Wuhan and Delta spike variants and show that dual expression of ACE2 with either neuropilin-2, ephrin receptor A7, solute carrier family 6 member 15, or myelin and lymphocyte protein 2 significantly enhances viral uptake. Collectively, our data show that SARS-CoV-2 synergistically engages several host factors for cell entry and establishes μMap as a powerful tool for rapidly interrogating host-virus interactomes.
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U2 - 10.1021/jacs.2c06806
DO - 10.1021/jacs.2c06806
M3 - Article
C2 - 36049228
AN - SCOPUS:85137864921
SN - 0002-7863
VL - 144
SP - 16604
EP - 16611
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 36
ER -