Photochemical Identification of Auxiliary Severe Acute Respiratory Syndrome Coronavirus 2 Host Entry Factors Using μMap.

TitlePhotochemical Identification of Auxiliary Severe Acute Respiratory Syndrome Coronavirus 2 Host Entry Factors Using μMap.
Publication TypeJournal Article
Year of Publication2022
AuthorsSuzuki, S, Geri, JB, Knutson, SD, Bell-Temin, H, Tamura, T, Fernández, DF, Lovett, GH, Till, NA, Heller, BL, Guo, J, MacMillan, DWC, Ploss, A
JournalJ Am Chem Soc
Volume144
Issue36
Pagination16604-16611
Date Published2022 Sep 14
ISSN1520-5126
KeywordsAngiotensin-Converting Enzyme 2, COVID-19, Humans, Pandemics, Peptidyl-Dipeptidase A, Protein Binding, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Virus Internalization
Abstract

<p>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 () was identified as the primary viral entry receptor, and transmembrane serine protease 2 primes the spike protein for membrane fusion. However, 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 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.</p>

DOI10.1021/jacs.2c06806
Alternate JournalJ Am Chem Soc
PubMed ID36049228
PubMed Central IDPMC9469761
Grant ListP30 CA072720 / CA / NCI NIH HHS / United States
R01 AI138797 / AI / NIAID NIH HHS / United States
F32 GM142206 / GM / NIGMS NIH HHS / United States
R01 AI153236 / AI / NIAID NIH HHS / United States
UL1 TR003017 / TR / NCATS NIH HHS / United States
R01 AI146917 / AI / NIAID NIH HHS / United States
R35 GM134897 / GM / NIGMS NIH HHS / United States
R01 AI107301 / AI / NIAID NIH HHS / United States