ArticleNature communications2021
Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 114 citations in OpenAlex.
- The CCR2 inflammatory pathway is a target for improving severe disease and pulmonary inflammation in experimental COVID-19.Virulence · 2026Article
- Development and characterization of mouse-adapted recombinant SARS-CoV-2 expressing reporter genes.Microbiology spectrum · 2026Article
- Article
- Molecular basis of fox ACE2 recognition by receptor binding domains of SARS-CoV-2 and PCoV-GD.Cell insight · 2026Article
- IFITM3 deficiency drives SARS-CoV-2 adaptation while preserving variant-specific traits.Nature communications · 2026Article
- Therapeutic applications of interface-mimicking peptides for targeting the SARS-CoV-2 NSP12-NSP8 RdRp complex.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Characterization of a SARS-CoV-2 infection model in golden hamsters with diabetes mellitus.Virologica Sinica · 2025Article
- Characterization of key spike RBD residues influencing SARS-CoV-2 variant adaptation to avian ACE2.Frontiers in cellular and infection microbiology · 2025Article
- The lethal K18-hACE2 knock-in mouse model mimicking the severe pneumonia of COVID-19 is practicable for antiviral development.Emerging microbes & infections · 2024Article
- Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality.Cell death and differentiation · 2024Article
- Lung repair and regeneration: Advanced models and insights into human disease.Cell stem cell · 2024Review
- Development of a Mouse-Adapted Reporter SARS-CoV-2 as a Tool for Two-Photon In Vivo Imaging.Viruses · 2024Article
- Influence of Environmental Factors and Genome Diversity on Cumulative COVID-19 Cases in the Highland Region of China: Comparative Correlational Study.Interactive journal of medical research · 2024Article
- SARS-CoV-2 rapidly evolves lineage-specific phenotypic differences when passaged repeatedly in immune-naïve mice.Communications biology · 2024Article
- Viral uptake and pathophysiology of the lung endothelial cells in age-associated severe SARS-CoV-2 infection models.Aging cell · 2024Article
- SARS-CoV-2 immunity in animal models.Cellular & molecular immunology · 2024Review
- Adaptation of SARS-CoV-2 to ACE2Journal of virology · 2024Article
- Exosomes derived from syncytia induced by SARS-2-S promote the proliferation and metastasis of hepatocellular carcinoma cells.Frontiers in cellular and infection microbiology · 2024Article
- Generation and characterization of a humanized ACE2 mouse model to study long-term impacts of SARS-CoV-2 infection.Journal of medical virology · 2024Article
- The Y498T499-SARS-CoV-2 spike (S) protein interacts poorly with rat ACE2 and does not affect the rat lung.Access microbiology · 2024Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 7 institutions in 2 countries.
Funding
Abstract
There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.