ml7b00364_si_001.pdf (798.91 kB)
Inhibition of Herpes Simplex Virus‑1 Entry into Human Cells by Nonsaccharide Glycosaminoglycan Mimetics
journal contribution
posted on 2018-07-16, 00:00 authored by Rahaman
Navaz Gangji, Nehru Viji Sankaranarayanan, James Elste, Rami A. Al-Horani, Daniel K. Afosah, Rachel Joshi, Vaibhav Tiwari, Umesh R. DesaiAlthough 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.