IPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections

James McNulty, Leonardo D'Aiuto, Yun Zhi, Lora McClain, Carlos Zepeda-Velázquez, Spencer Ler, Hilary A. Jenkins, Michael B. Yee, Paolo Piazza, Robert H. Yolken, Paul R. Kinchington, Vishwajit L. Nimgaonkar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)46-50
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume7
Issue number1
DOIs
StatePublished - Jan 14 2016

Keywords

  • Amaryllidaceae
  • HSV-1
  • Herpesvirus
  • alkaloid
  • stem cells
  • varicella zoster

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    McNulty, J., D'Aiuto, L., Zhi, Y., McClain, L., Zepeda-Velázquez, C., Ler, S., Jenkins, H. A., Yee, M. B., Piazza, P., Yolken, R. H., Kinchington, P. R., & Nimgaonkar, V. L. (2016). IPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections. ACS Medicinal Chemistry Letters, 7(1), 46-50. https://doi.org/10.1021/acsmedchemlett.5b00318