Site-Specific Entry Factors Define Cellular Susceptibility to SARS-CoV-2 in Human Tissues
Year: 2026
Type: preprint
Abstract: SUMMARY SARS-CoV-2 primarily infects the respiratory epithelium through entry factors ACE2 and TMPRSS2. However, alternative viral entry receptors and/or modulators of viral entry factors expression may contribute to infection in respiratory as well as non-respiratory tissues, including the kidneys and colon. Using single-cell analyses, we identified novel candidates for spike-mediated viral entry in epithelial cells from diverse fresh human tissues exposed to a labeled spike-pseudotyped virus. Systematic viral tracking revealed tissue-specific membrane receptors that contribute to viral entry, functionally validated in human tissues and partially predicted by molecular modeling. We found ADAM17 and IL1R1, together with canonical molecules, to significantly facilitate viral entry in the lung parenchyma, while entry into the renal cortex was less dependable on canonical factors, but strongly modulated by JAK1/2 engagement. These findings uncover distinct viral entry mechanisms across tissues and suggest novel organ-specific therapeutic targets for patients at risk.
Authors: Mireia Vivas Roca, Cristina Mancebo-Pérez, Mohmed Abdalfttah, Ismael Balafkir, Aleix Benítez-Martínez, Víctor Montal, Alba González, Irene Mota-Gómez, Judith Grau-Expósito, Daan KJ Pieren, Bibiana Planas, Joel Rosado, María Eugenia Semidey, Stefania Landolfi, Eloy Espín-Bassany, Enric Trilla, Vicenç Falcó, Adrià Curran, Joaquín Burgos, María J Buzon, Víctor Guallar, Holger Heyn, Meritxell Genescà
Institutions: Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Centro Nacional de Análisis Genómico, Barcelona Supercomputing Center, Universitat de Barcelona, University Medical Center Utrecht, Institució Catalana de Recerca i Estudis Avançats
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7160702601