DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

• DOI: 10.1371/journal.ppat.1009576
• Publication Date: 2021-05-20T17:30:07Z
• Authors: Michel Thépaut; Joanna Luczkowiak; Corinne Vivès; Nuria Labiod; Isabelle Bally; Fátima Lasala; Yasmina Grimoire; Daphna Fenel; Sara Sattin; Nicole Thielens; Guy Schoehn; Anna Bernardi; Rafael Delgado; Franck Fieschi
• Keywords: 0301 basic medicine; QH301-705.5; Receptors, Cell Surface; 612; Respiratory Mucosa; [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry; Cell Line; Jurkat Cells; 03 medical and health sciences; Antigens, CD; Chlorocebus aethiops; Animals; Humans; Lectins, C-Type; Biology (General); Lung; Vero Cells; [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]; Molecular Biology/Structural Biology [q-bio.BM]; SARS-CoV-2; COVID-19; RC581-607; 3. Good health; Mannose-Binding Lectins; Mannosides; Spike Glycoprotein, Coronavirus; glycomimetics; DC-SIGN; Covid-19; SARS-CoV2;; Immunologic diseases. Allergy; Cell Adhesion Molecules; Research Article; Protein Binding

The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.