A dihydro-pyrido-indole potently inhibits HSV-1 infection by interfering the viral immediate early transcriptional events

Paromita Bag, Durbadal Ojha, Hemanta Mukherjee, Umesh C. Halder, Supriya Mondal, Aruna Biswas, Ashoke Sharon, Luc Van Kaer, Sekhar Chakrabarty, Gobardhan Das, Debashis Mitra, Debprasad Chattopadhyay

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

In our continued quest for identifying novel molecules from ethnomedicinal source we have isolated an alkaloid 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3, 4-b]indole, also known as Harmaline (HM), from an ethnomedicinal herb Ophiorrhiza nicobarica. The compound exhibited a potent anti-HSV-1 activity against both wild type and clinical isolates of HSV-1. Further we demonstrated that HM did not interfere in viral entry but the recruitment of lysine-specific demethylase-1 (LSD1) and the binding of immediate-early (IE) complex on ICP0 promoter. This leads to the suppression of viral IE gene synthesis and thereby the reduced expression of ICP4 and ICP27. Moreover, HM at its virucidal concentration is nontoxic and reduced virus yields in cutaneously infected Balb/C mice. Thus, the interference in the binding of IE complex, a decisive factor for HSV lytic cycle or latency by HM reveals an interesting target for developing non-nucleotide antiherpetic agent with different mode of action than Acyclovir.

Original languageEnglish (US)
Pages (from-to)126-134
Number of pages9
JournalAntiviral Research
Volume105
Issue number1
DOIs
StatePublished - May 2014

Keywords

  • Ethnomedicine
  • HSV
  • Immediate-early transcription
  • LSD1
  • Ophiorrhiza nicobarica

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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