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iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections
James McNulty1, Leonardo D'Aiuto2, Yun Zhi2
1Department of Chemistry and Chemical-Biology, McMaster University , 1280 Main Street, West Hamilton, Ontario L8S 4M1, Canada.
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.
