Host immune receptors recognizing SARS-CoV-2 spike protein

Host immune receptors recognizing the SARS-CoV-2 spike protein are a diverse group of pattern recognition receptors (PRRs) and cell-surface molecules that identify the viral spike (S) glycoprotein to initiate or modulate the host immune response. This group includes Toll-like receptors, notably TLR4 and TLR2, which recognize the S1 and S2 subunits of the spike protein to trigger the NF-κB signaling pathway and the subsequent release of pro-inflammatory cytokines such as IL-6 and TNF-α (Zhao et al., 2021; Khan et al., 2021). Additionally, C-type lectin receptors (CLRs) such as DC-SIGN (CD209), L-SIGN (CLEC4M), and MGL (CLEC10A) bind to the glycans on the spike protein, potentially acting as alternative attachment factors that facilitate viral entry or promote the infection of susceptible cells (Amraei et al., 2021; Lu et al., 2021). While these interactions are essential for the innate detection of the pathogen, their dysregulation is a major contributor to the hyper-inflammatory state or "cytokine storm" observed in severe COVID-19 cases (Nature Reviews Immunology, 2021). Therapeutic strategies targeting these receptors, such as the TLR4 antagonist Eritoran or various experimental glycomimetics, aim to dampen pathological inflammation and block non-ACE2 mediated viral pathways. These interventions must be carefully balanced to reduce tissue damage without compromising the host's ability to clear the viral infection.

Other names

Pattern recognition receptors (PRRs)SARS-CoV-2 spike-binding immune receptorsToll-like receptor 4 (TLR4)Toll-like receptor 2 (TLR2)Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN/CD209)Liver/lymph node-specific ICAM-3-grabbing non-integrin (L-SIGN/CLEC4M)Macrophage galactose-type lectin (MGL/CLEC10A)Sialic acid-binding Ig-like lectin 1 (Siglec-1/CD169)

Competitive antagonism of pattern recognition receptors to block viral protein-induced inflammatory signaling and inhibit lectin-mediated viral attachment.