ArticleHepatic medicine : evidence and research2021
Binding of the SARS-CoV-2 Spike Protein to the Asialoglycoprotein Receptor on Human Primary Hepatocytes and Immortalized Hepatocyte-Like Cells by Confocal Analysis.
Article in Hepatic medicine : evidence and research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 17 citations in OpenAlex.
- SARS-CoV-2 Assembly: Gaining Infectivity and Beyond.Viruses · 2024Review
- Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes.Signal transduction and targeted therapy · 2024Article
- Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.Molecular aspects of medicine · 2023Review
- How the Competition for Cysteine May Promote Infection of SARS-CoV-2 by Triggering Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Article
- Non-alcoholic fatty liver disease and COVID-19: Harmless companions or disease intensifier?World journal of gastroenterology · 2023Review
- Analysis of SARS-CoV-2 Variant-Specific Serum Antibody Post-Vaccination Utilizing Immortalized Human Hepatocyte-Like Cells (HLC) to Assess Development of Immunity.Hepatic medicine : evidence and research · 2023Article
- Structure genomics of SARS-CoV-2 and its Omicron variant: drug design templates for COVID-19.Acta pharmacologica Sinica · 2022Review
- SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19.International journal of molecular sciences · 2022Review
- Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19.World journal of hepatology · 2021Review
- Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response.Virology journal · 2021Article
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2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe SARS-CoV-2 virus may have direct or indirect effects on other human organs beyond the respiratory system and including the liver, via binding of the spike protein. This study investigated the potential direct interactions with the liver by comparing the binding of SARS-CoV-2 spike proteins to human AT2-like cells, primary human hepatocytes and immortalized hepatocyte-like hybrid cells. Receptors with binding specificity for SARS-CoV-2 spike protein on AT2 cells and hepatocytes were identified.
methodsThe specific binding of biotinylated spike and spike 1 proteins to undifferentiated human E12 MLPC (E12), E12 differentiated alveolar type 2 (AT2) cells, primary human hepatocytes (PHH) and E12 human hepatocyte-like hybrid cells (HLC) was studied by confocal microscopy. We investigated the expression of ACE-2, binding of biotinylated spike protein, biotinylated spike 1 and inhibition of binding by unlabeled spike protein, two neutralizing antibodies and an antibody directed against the hepatocyte asialoglycoprotein receptor 1 (ASGr1).
resultsE12 MLPC did not express ACE-2 and did not bind either of spike or spike 1 proteins. AT2-like cells expressed ACE-2 and bound both spike and spike 1. Both PHH and HLC did not express ACE-2 and did not bind spike 1 protein. However, both PHH and HLC actively bound the spike protein. Biotinylated spike protein binding was inhibited by unlabeled spike but not spike 1 protein on PHH and HLC. Two commercial neutralizing antibodies blocked the binding of the spike to PHH and HLC but only one blocked binding to AT2. An antibody to the hepatocyte ASGr1 blocked the binding of the spike protein to PHH and HLC.
conclusionThe absence of ACE-2 receptors and inhibition of spike binding by an antibody to the ASGr1 on both PHH and HLC suggested that the spike protein interacts with the ASGr1. The differential antibody blocking of spike binding to AT2, PHH and HLC indicated that neutralizing activity of SARS-CoV-2 binding might involve additional mechanisms beyond RBD binding to ACE-2.
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