Cellular glycans play key roles in the infection process of many human
viruses. Viral attachment to heparan sulfate (HS) or sialic acid (SA) moieties in cell
surface glycans is a critical and conserved step for the entry of many human viruses,
including clinically important human pathogens such as hepatitis B virus, hepatitis C
virus, human immunodeficiency virus and influenza virus. As such, glycans are
attractive targets for broadly acting antivirals. Molecules that mimic HS or SA interfere
with viral attachment by competing for binding of virion glycoproteins to cellular
glycans. Modulation of the levels of cellular glycans also affects viral attachment.
These approaches show great promise based on their broad-spectrum activities, but the
molecules identified so far often possess undesirable pharmacological properties
resulting in potential adverse effects. Here, we describe the mechanisms involved in
glycan binding, discuss broadly acting glycan-targeted antiviral strategies, and provide
perspectives for the rational design of broad-spectrum small molecule entry inhibitors
with broad-spectrum activities and appropriate pharmacological properties.
Keywords: Antivirals, Broad-spectrum antiviral therapy, Chemical biology,
Glycan mimetics, Glycosaminoglycans, Glycotherapy, Heparan sulfate proteoglycans,
Heparin, Hepatitis B virus, Hepatitis C virus, Herpes simplex virus, Human immunodeficiency virus, Influenza virus, Polyphenols, Sialic acid, Sialoglycans,
Small molecule entry inhibitors, Viral attachment, Viral entry, Virus-host interactions.
