Marine-derived sulfated glycans display a potent virostatic mechanism to block herpes simplex virus type-1 (HSV-1) entry and spread

Description:

A naturally derived library of glycomimetic mimicking the structure-function of heparan sulfate (HS) remains an untapped reservoir for drug discovery against viral infections. In this work we screened a library of marinederived sulfated glycans from seaweeds and sea cucumbers to investigate if they can compete for the ligand/ receptor binding sites to prevent virus entry. Multiple promising candidates were identified, such as RPI-27 (IC50: 1.51 μ M), FCS-Pg (IC50: 0.906 μ M), FCS-Ib (IC50: 0.725 μ M), and Rhamnan sulfate (RS; IC50: 0.499 μ M) capable of preventing HSV-1 entry at non-toxic concentrations when pre-incubated with the target cells before infection. Interestingly, we noticed a significant improvement in the IC50 values among the sulfated glycans [RPI-27 (IC50: 0.008 μ M), FCS-Pg (IC50: 0.007 μ M), FCS-Ib (IC50: 0.003 μ M), and RS (IC50: 0.004 μ M)] when they were preexposed to the virus before infecting to the target cell. The Surface Plasmon Resonance (SPR) spectroscopy established the library's efficacy for their high binding affinity for HSV-1 central envelope glycoprotein D (gD), implying the potent virostatic nature of the sulfated glycans. These findings offer a rationalized development of targeted and fine-tuned marine-derived carbohydrate-based molecules to prevent HSV-1 entry and virus replication using either prophylaxis and or treatment approaches.

Publications:

• James Elste; Michele Rabbitt; Chunyu Wang; Jonathan S. Dordick; Vaibhav Tiwari; Fuming Zhang; Marine-derived sulfated glycans display a potent virostatic mechanism to block herpes simplex virus type-1 (HSV-1) entry and spread; Carbohydrate Polymers, 2025

Tags:

Carbohydrates Glycosaminoglycans Immunology Surface plasmon resonance

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