Project description:The continued evolution of SARS-CoV-2 has produced variants with enhanced transmissibility despite reduced binding affinity to the canonical entry receptor ACE2, suggesting the involvement of additional host factors. Here, we integrate large-scale sequence analysis, structure-informed machine learning, biochemical assays, cell-based entry models, and in vivo infection studies to examine receptor usage diversification in recent SARS-CoV-2 variants. We find that multiple post-Omicron lineages, including XBB-derived variants, exhibit increased functional engagement of dipeptidyl peptidase 4 (DPP4), accompanied by reduced reliance on ACE2-mediated entry in defined experimental contexts. In human DPP4 knock-in mice, representative XBB variants display enhanced replication with limited pulmonary pathology. Together, these findings support a model in which SARS-CoV-2 evolution is characterized by diversification of receptor engagement strategies, highlighting DPP4 as a functionally relevant entry factor that may contribute to viral fitness under immune pressure.

2026-04-28 | GSE328992 | GEO

Comparative analyses of ACE2 and TMPRSS2 gene: Implications for the risk to which vertebrate animals are susceptible to SARS-CoV-2.

Project description: Not available

| S-EPMC8242802 | biostudies-literature

CRISPRa screen with SARS-CoV-2 authentic virus in HEK293-ACE2

Project description:These studies used CRISPR-activation in order to identify genes that could confer increased survival to SARS-CoV-2. To do this, a clonal cell line expressing ACE2 and CRISPR-activation (Suntag) machinery was engineered. Then the Weismann library of activating guides was used to infect these populations at a ~2000 coverage. Diversity and experimental controls were used for analysis

2025-09-02 | GSE240991 | GEO

Binding of SARS-COV-2 (COVID-19) and SARS-COV to human ACE2: Identifying binding sites and consequences on ACE2 stiffness.

Project description: Not available

| S-EPMC8420131 | biostudies-literature

RNAseq analyses in HEK293T-ACE2 cells infected with SARS-CoV-2 (VOC Delta, 24hours) vs untreated cells

Project description:In this study a gene expression (i.e., RNAseq) analysis was performed in HEK293T-ACE2 cellular model upon infection with viral particle belonging to VOC Delta (MOI: 0.026) for 24 hours in order to have a global picture of the transcriptome landscape in response to early phase of infection of SARS-CoV-2 ( VOC Delta infection and to evaluate the role of Ca2+ in HEK293-ACE2 cellular model and transfer to homeostasis in SARS-COV-2 patients (by Pasqualino de Antonellis1-2* and Veronica Ferrucci 1-2* (first authors) et al. and Massimo Zollo1-2# (corresponding author). Manuscript in preparation 2022 July 15th 2022. Short title "ATP2B1 (PMCA1), regulated by FOXO3, influences susceptibility to severe COVID19".

2022-12-01 | E-MTAB-11973 | biostudies-arrayexpress

Human ACE2 Genetic Polymorphism Affecting SARS-CoV and SARS-CoV-2 Entry into Cells.

Project description: Not available

| S-EPMC9430119 | biostudies-literature

Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?

Project description: Not available

| S-EPMC7433338 | biostudies-literature

ACE2: the molecular doorway to SARS-CoV-2.

Project description: Not available

| S-EPMC7772801 | biostudies-literature