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

Autor:	Gangji RN; Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219, United States., Sankaranarayanan NV; Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219, United States.; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States., Elste J; Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois 60515, United States., Al-Horani RA; Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219, United States.; College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125, United States., Afosah DK; Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219, United States.; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States., Joshi R; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States., Tiwari V; Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois 60515, United States., Desai UR; Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219, United States.; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2018 Jul 16; Vol. 9 (8), pp. 797-802. Date of Electronic Publication: 2018 Jul 16 (Print Publication: 2018).
DOI:	10.1021/acsmedchemlett.7b00364
Abstrakt:	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. Competing Interests: The authors declare no competing financial interest.
Databáze:	MEDLINE
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