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Inhibition of Herpes Simplex Virus-1 Entry into Human Cells by Nonsaccharide Glycosaminoglycan Mimetics. 2018

Rahaman Navaz Gangji, and Nehru Viji Sankaranarayanan, and James Elste, and Rami A Al-Horani, and Daniel K Afosah, and Rachel Joshi, and Vaibhav Tiwari, and Umesh R Desai
Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219, United States.

Although heparan sulfate (HS) has been implicated in facilitating entry of enveloped viruses including herpes simplex virus (HSV), small molecules that effectively compete with this abundant, cell surface macromolecule remain unknown. We reasoned that entry of HSV-1 involving its glycoprotein D (gD) binding to HS could be competitively targeted through small, synthetic, nonsaccharide glycosaminoglycan mimetics (NSGMs). Screening a library of NSGMs identified a small, distinct group that bound gD with affinities of 8-120 nM. Studies on HSV-1 entry into HeLa, HFF-1, and VK2/E6E7 cells identified inhibitors with potencies in the range of 0.4-1.0 μM. These synthetic NSGMs are likely to offer promising chemical biology probes and/or antiviral drug discovery opportunities.

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