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

Int J Mol Sci. 2022 Aug 30;23(17):9842. doi: 10.3390/ijms23179842.

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.

Keywords: Heparan sulfates; glycoconjugates; sialic acid; viral entry; virus receptors.

Publication types

  • Review

MeSH terms

  • COVID-19*
  • Glycoconjugates / metabolism
  • Heparitin Sulfate / metabolism
  • Humans
  • N-Acetylneuraminic Acid / metabolism
  • Receptors, Virus / metabolism
  • SARS-CoV-2
  • Sialic Acids / metabolism
  • Sulfates
  • Virus Attachment
  • Viruses* / metabolism

Substances

  • Glycoconjugates
  • Receptors, Virus
  • Sialic Acids
  • Sulfates
  • Heparitin Sulfate
  • N-Acetylneuraminic Acid

Grants and funding

This research was supported by Dirección General de Asuntos del Personal Académico (DGAPA) of the UNAM for the Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) grant number IN224820.