Abstract

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.