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. 2021 Nov 18;195:114847. doi: 10.1016/j.bcp.2021.114847

Fig. 1.

Fig. 1

Therapeutic targeting of Siglecs in COVID-19. (A) Viral capture and uptake by Siglec-1 on myeloid antigen presenting cells (APCs) leads to cytokine storm and viral propagation. Anti-Siglec-1 monoclonal antibodies (mAbs) can block uptake of SARS-CoV-2 and inhibit trans-infection of target cells expressing ACE2/TMPRSS2 [19]. (B) SARS-CoV-2 pathogen/damage-associated molecular pattern (PAMP and DAMP)-mediated pattern recognition receptor (PRR) stimulation leads to production of pro-inflammatory neutrophil extracellular traps (NETosis), that propagate the hyperinflammatory cascade in COVID-19. Synthetic Siglec-9 agonists can trigger clustering of Siglec-9 receptors on neutrophils and suppress NETosis and associated inflammation in COVID-19 [108]. (C) Association of CD24 or CD52 with Siglec-10 inhibits PAMP/DAMP-PRR-mediated inflammatory responses. CD24Fc and CD24 exosomes may act through Siglec stimulation to protect against severe COVID-19 [[118], [119]]. Treatment with anti-human CD52 antibody is associated with mild COVID-19 symptoms and may also act through Siglec stimulation [116]. (D) Increased levels of neuraminidase 1 (Neu1) enzyme in severe COVID-19 may prevent protective Siglec activation through cleavage of sialic acid (SA) residues on CD24/CD52. Treatment with Neu inhibitors Oseltamivir or Zanamivir reduces SA shedding and neutrophil overactivation in COVID-19 patients [128].