Heparan Sulfate and Sialic Acid in Viral Attachment: Two Sides of the Same Coin?

Abstract

Sialic acids and heparan sulfates make up the outermost part of the cell membrane and the extracellular matrix. Both structures are characterized by being negatively charged, serving as receptors for various pathogens, and are highly expressed in the respiratory and digestive tracts. Numerous viruses use heparan sulfates as receptors to infect cells; in this group are HSV, HPV, and SARS-CoV-2. Other viruses require the cell to express sialic acids, as is the case in influenza A viruses and adenoviruses. This review aims to present, in a general way, the participation of glycoconjugates in viral entry, and therapeutic strategies focused on inhibiting the interaction between the virus and the glycoconjugates. Interestingly, there are few studies that suggest the participation of both glycoconjugates in the viruses addressed here. Considering the biological redundancy that exists between heparan sulfates and sialic acids, we propose that it is important to jointly evaluate and design strategies that contemplate inhibiting the interactions of both glycoconjugates. This approach will allow identifying new receptors and lead to a deeper understanding of interspecies transmission.

Antiviral activity of marine sulfated glycans against pathogenic human coronaviruses

“…This was the only noncoronavirus enveloped virus tested in this work. It is possible to hypothesize that the structural requirement for the glycans on the host cells are different among the coronavirus spike proteins and IAV HA 13 , in which sialic acid, as opposed to the role of HS in coronaviral infectivity 11 , plays a key role in IAV infectivity 14 . This lack of activity against IAV may also be due to an incomplete broad-spectrum antiviral activity as seen previously.…”

SARS‐CoV‐2, periodontal pathogens, and host factors: The trinity of oral post‐acute sequelae of COVID‐19

“…[129][130][131][132][133] Heparan sulphate can interact with a variety of ligands mediating additional receptor activations. 134 Some membrane receptors are also regulatory for cell-to-cell communication, tissue integrity, oral mucosal infection, inflammatory and neoplasia responses associated with pathogen pattern recognition (e.g., pattern recognition receptor, PRR) producing an amplification of transcriptional inflammatory signalling through NF-kB leading to cytokine expressions. 135,136 HSPG receptor expression also cooperates with surface glycoproteins such as glycans, which are supportive attachment domains in the PS family of receptors.…”

“…Both cell structures are characterised by a negative charge facilitating adherence of oral pathogens, which include a variety of microbes including oral viruses such as HPV, HHV, and SARS‐CoV‐2, all likely etiologic agents of oral diseases such as PD, oral pharyngitis, mucositis, xerostomia, dysgeusia, dysphagia, vesicular‐bullae disorders, keratotic lesions, dental pulpitis, and a variety of acute and chronic inflammatory presentations 129–133 . Heparan sulphate can interact with a variety of ligands mediating additional receptor activations 134 . Some membrane receptors are also regulatory for cell‐to‐cell communication, tissue integrity, oral mucosal infection, inflammatory and neoplasia responses associated with pathogen pattern recognition (e.g., pattern recognition receptor, PRR) producing an amplification of transcriptional inflammatory signalling through NF‐kB leading to cytokine expressions 135,136 …”

Myocardial Oedema as a Consequence of Viral Infection and Persistence – a Narrative Review with Focus on COVID-19 and Post COVID Sequelae

“…heparan sulphate, sialic acid [381] Human herpesvirus 1, 6 heparan sulphate, syndecan-1 [382,383] Epstein-Barr virus glycoproteins, hyaluronan synthesis [384,385] Human cytomegalovirus heparan sulphate [386,387] Enteroviruses heparan sulphate, P-selectin glycoprotein ligand-1, sialylated glycan [388][389][390] Adenovirus heparan sulphate, sialic acid [391][392][393] Hepatitis C virus heparan sulphate, syndecan-1 [394,395] SARS-CoV-2 heparan sulphate proteoglycans [223,396] Influenza virus sialic acids, hyaluronan synthesis [391,397]…”