Preferential recognition and antagonism of SARS-CoV-2 spike glycoprotein binding to 3--sulfated heparan sulfate.

The COVID-19 pandemic caused by SARS-CoV-2 is in immediate need of an effective antidote. Although the Spike glycoprotein (SgP) of SARS-CoV-2 has been shown to bind to heparins, the structural features of this interaction, the role of a plausible heparan sulfate proteoglycan (HSPG) receptor, and the antagonism of this pathway through small molecules remain unaddressed. Using an cellular assay, we demonstrate HSPGs modified by the 3--sulfotransferase isoform-3, but not isoform-5, preferentially increased SgP-mediated cell-to-cell fusion in comparison to control, unmodified, wild-type HSPGs.

Discovering small-molecule therapeutics against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health pandemic. The lack of effective treatments, coupled with its etiology, has resulted in more than 400,000 deaths at the time of writing. The SARS-CoV-2 genome is highly homologous to that of SARS-CoV, the causative agent behind the 2003 SARS outbreak.

Sulfotransferase and Heparanase: Remodeling Engines in Promoting Virus Infection and Disease Development.

An extraordinary binding site generated in heparan sulfate (HS) structures, during its biosynthesis, provides a unique opportunity to interact with multiple protein ligands including viral proteins, and therefore adds tremendous value to this master molecule. An example of such a moiety is the sulfation at the C3 position of glucosamine residues in HS chain via 3- sulfotransferase (3-ST) enzymes, which generates a unique virus-cell fusion receptor during herpes simplex virus (HSV) entry and spread. Emerging evidence now suggests that the unique patterns in HS sulfation assist multiple viruses in invading host cells at various steps of their life cycles.