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Authors:Gao et al 

Journal/ Pre-Print:bioRxiv 

TagsCell Biology, Immunology/Immunity, Inflammation, Molecular biology 

Research Highlights 

  1. Identification of C-type lectin receptors that bind SARS-CoV-2 S protein in a glycan-dependent manner 

  1. Expression levels of DC-SIGN and MGL on macrophages and dendritic cells increase in severe COVID-19 patients 

Summary 

Gao et al aimed to characterise the connection between the glycosylation pattern of the spike protein S and recognition by glycan-binding pattern recognition receptors. They identified C-type lectin receptors (CLRs) DC-SIGN, L-SIGN, MR and MGL as binding to SARS-CoV-2 via different glycans. DC-SIGN, MR and MGL had a strong binding affinity for S protein. By glycomics it was confirmed that the glycans on SARS-CoV-2 could serve as ligands for the CRLs mentioned above. Furthermore, by interrogating existing scRNA-seq data of COVID-19 patients, they confirmed expression of CRLs in resident immune cells and an increase in expression levels of DC-SIGN and MGL in severe COVID-19 patients. By blocking CRL receptors, SARS-CoV-2 spread might be attenuated and immune cell hyperactivation limited. 

Impact for SARS-CoV2/COVID19 research efforts  

Understand the virology and/or cell biology of SARS-CoV2/COVID19: looking at the glycosylation pattern of SARS-CoV-2 and its recognition by innate immune receptors 

Study Type  

  • In silico study / bioinformatics study 

  • In vitro study 

Strengths and limitations of the paper 

Novelty: SARS-CoV-2 is recognised in a glycan-dependent manner by various innate immune receptors, new O-glycosylation sites discovered  

Standing in the field:Glycosylation pattern of full SARS-CoV-2 published previously, connection with innate immune receptors not uncovered 

Appropriate statistics: Statistics not applicable, but in the one case where they applied it, they did not describe the test used 

Viral model used:Recombinant full-length S-protein produced by HEK293 cells 

Translatability:Recognition and internalisation by innate immune cells as an alternative interaction route of SARS-CoV-2, leading to pathological cytokine storm, potential new therapeutic avenues (blocking these receptors) 

Main limitations: In vitro study, might not reflect mucosal environment (especially as Vero E6 cells are used for SARS-CoV-2 internalisation), ACE2 still has a much higher affinity for SARS-CoV-2 than the CRLs, only part of the virus used (whereas with complete virus there could be masking of some of the glycosylation sites), results of SARS-Cov-2 binding (pathway activation/cytokine secretion) only by correlation with scRNA-seq dataset