Coronaviruses: Is Sialic Acid a Gate to the Eye of Cytokine Storm? From the Entry to the Effects

Abstract

Coronaviruses (CoVs) are a diverse family of the enveloped human and animal viruses reported as causative agents for respiratory and intestinal infections. The high pathogenic potential of human CoVs, including SARS-CoV, MERS-CoV and SARS-CoV-2, is closely related to the invasion mechanisms underlying the attachment and entry of viral particles to the host cells. There is increasing evidence that sialylated compounds of cellular glycocalyx can serve as an important factor in the mechanism of CoVs infection. Additionally, the sialic acid-mediated cross-reactivity with the host immune lectins is known to exert the immune response of different intensity in selected pathological stages. Here, we focus on the last findings in the field of glycobiology in the context of the role of sialic acid in tissue tropism, viral entry kinetics and immune regulation in the CoVs infections.

Keywords: MERS-CoV; SARS-CoV; SARS-CoV-2; Siglec; coronavirus; sialic acid.

Figure 1

Receptor recognition pattern during the CoVs infections. The CoVs invade host cells through the attachment, binding and entry mechanism based on the sialic acid and protein receptors. After sialic acid-mediated virus attachment and its spike protein activation by transmembrane serine protease 2 (TMPRSS2), the entry event is associated with the binding of specific protein receptor: ACE-2 (angiotensin converting enzyme type 2); DPP4 (dipeptidyl peptidase 4); APN (aminopeptidase N). The ability to recognize sialoglycans determines virus tissue tropism and clinical manifestations among infected organs.

Figure 2

The possible effects of the CoVs targeting to Siglecs. The viral envelope glycans interact with sialic acid-binding lectins expressed in the host cell-dependent manner. Depending on the individual Siglec expression profile, the interactions with the viral sialic acid ligands exerts the immune response of different intensity. Abbreviations: DAP12-DNAX activation protein of 12 kDa; Syk-spleen tyrosine kinase; SHP-1-Src homology region 2 domain-containing phosphatase-1; SHP-2-Src homology region 2 domain-containing phosphatase-2.