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

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.

• Authors: 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
• Journal: Antiviral research (Antiviral Res) Vol. 105 Pg. 126-34 (May 2014) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 24576908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• ICP27 protein, human herpesvirus 1
• Immediate-Early Proteins
• herpes simplex virus, type 1 protein ICP4
• Harmaline

Topics

• Animals
• Antiviral Agents (isolation & purification, pharmacology, therapeutic use)
• Disease Models, Animal
• Female
• Harmaline (isolation & purification, pharmacology, therapeutic use)
• Herpes Simplex (drug therapy, virology)
• Herpesvirus 1, Human (drug effects, genetics)
• Immediate-Early Proteins (antagonists & inhibitors, biosynthesis)
• Mice, Inbred BALB C
• Rubiaceae (chemistry)
• Transcription, Genetic (drug effects)