title: iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections.
abstract: The Amaryllidaceae alkaloid trans-dihydrolycoricidine 7 and three analogues 8-10 were produced via asymmetric chemical synthesis. Alkaloid 7 proved superior to acyclovir, the current standard for herpes simplex virus, type 1 (HSV-1) infection. Compound 7 potently inhibited lytic HSV-1 infection, significantly reduced HSV-1 reactivation, and more potently inhibited varicella zoster virus (VZV) lytic infection. A configurationally defined (3R)-secondary alcohol at C3 proved crucial for efficacious inhibition of lytic HSV-1 infection.
authors.affiliation: Department of Chemistry and Chemical-Biology, McMaster University , 1280 Main Street, West Hamilton, Ontario L8S 4M1, Canada.
authors.forename: James
authors.initials: J
authors.lastname: McNulty
authors.affiliation: Department of Psychiatry, University of Pittsburgh, School of Medicine , 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213, United States.
authors.forename: Leonardo
authors.initials: L
authors.lastname: D'Aiuto
authors.affiliation: Department of Psychiatry, University of Pittsburgh, School of Medicine , 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhi
authors.affiliation: Department of Psychiatry, University of Pittsburgh, School of Medicine, 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213, United States; Department of Human Genetics, University of Pittsburgh, Graduate School of Public Health, 130 De Soto Street, Pittsburgh, Pennsylvania 15213, United States.
authors.forename: Lora
authors.initials: L
authors.lastname: McClain
authors.affiliation: Department of Chemistry and Chemical-Biology, McMaster University , 1280 Main Street, West Hamilton, Ontario L8S 4M1, Canada.
authors.forename: Carlos
authors.initials: C
authors.lastname: Zepeda-Velázquez
authors.affiliation: Department of Chemistry and Chemical-Biology, McMaster University , 1280 Main Street, West Hamilton, Ontario L8S 4M1, Canada.
authors.forename: Spencer
authors.initials: S
authors.lastname: Ler
authors.affiliation: Department of Chemistry and Chemical-Biology, McMaster University , 1280 Main Street, West Hamilton, Ontario L8S 4M1, Canada.
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Jenkins
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine , 203 Lothrop Street, Pittsburgh Pennsylvania 15213, United States.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yee
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Graduate School of Public Health , 130 De Soto Street, Pittsburgh, Pennsylvania 15213, United States.
authors.forename: Paolo
authors.initials: P
authors.lastname: Piazza
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine , 600 North Wolfe Street, Baltimore, Maryland 21287, United States.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine , 203 Lothrop Street, Pittsburgh Pennsylvania 15213, United States.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kinchington
authors.affiliation: Department of Psychiatry, University of Pittsburgh, School of Medicine, 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213, United States; Department of Human Genetics, University of Pittsburgh, Graduate School of Public Health, 130 De Soto Street, Pittsburgh, Pennsylvania 15213, United States.
authors.forename: Vishwajit L
authors.initials: VL
authors.lastname: Nimgaonkar
keywords: Amaryllidaceae; HSV-1; Herpesvirus; alkaloid; stem cells; varicella zoster
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