biostudies-literatureMiluzio AAssociazione Italiana per la Ricerca sul CancroFondazione Romeo ed Enrica Invernizzi104390https://www.ebi.ac.uk/biostudies/studies/S-EPMC9795807biostudies-literatureUnknown87<h4>Background</h4>The COVID-19 pandemic is an infectious disease caused by SARS-CoV-2. The first step of SARS-CoV-2 infection is the recognition of angiotensin-converting enzyme 2 (ACE2) receptors by the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein. Although the molecular and structural bases of the SARS-CoV-2-RBD/hACE2 interaction have been thoroughly investigated in vitro, the relationship between hACE2 expression and in vivo infection is less understood.<h4>Methods</h4>Here, we developed an efficient SARS-CoV-2-RBD binding assay suitable for super resolution microscopy and simultaneous hACE2 immunodetection and mapped the correlation between hACE2 receptor abundance and SARS-CoV-2-RBD binding, both in vitro and in human lung biopsies. Next, we explored the specificEBioMedicineMapping of functional SARS-CoV-2 receptors in human lungs establishes differences in variant binding and SLC1A5 as a viral entry modulator of hACE2.PMC979580726178Scagliola AOliveto SManfrini NPesce EConti MManganaro LRicciardi SBiffo SCordiglieri CAbrignani SFasciani ATerracciano LDe Francesco RCuomo AToccafondi MDonnici LGrifantini RBombaci MMiluzio AfalseMapping of functional SARS-CoV-2 receptors in human lungs establishes differences in variant binding and SLC1A5 as a viral entry modulator of hACE2.<h4>Background</h4>The COVID-19 pandemic is an infectious disease caused by SARS-CoV-2. The first step of SARS-CoV-2 infection is the recognition of angiotensin-converting enzyme 2 (ACE2) receptors by the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein. Although the molecular and structural bases of the SARS-CoV-2-RBD/hACE2 interaction have been thoroughly investigated in vitro, the relationship between hACE2 expression and in vivo infection is less understood.<h4>Methods</h4>Here, we developed an efficient SARS-CoV-2-RBD binding assay suitable for super resolution microscopy and simultaneous hACE2 immunodetection and mapped the correlation between hACE2 receptor abundance and SARS-CoV-2-RBD binding, both in vitro and in human lung biopsies. Next, we explored the specific2023-01-01T00:00:00Z2023 Jan2026-05-29T04:35:47.715Z2024-12-04T03:30:31.375ZS-EPMC97958073658459510.1016/j.ebiom.2022.104390