title: 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.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr. Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Paromita
authors.initials: P
authors.lastname: Bag
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr. Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Durbadal
authors.initials: D
authors.lastname: Ojha
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr. Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Hemanta
authors.initials: H
authors.lastname: Mukherjee
authors.affiliation: Virology Laboratory, National Institute of Cholera & Enteric Diseases, Kolkata, India.
authors.forename: Umesh C
authors.initials: UC
authors.lastname: Halder
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr. Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Supriya
authors.initials: S
authors.lastname: Mondal
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr. Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Aruna
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Department of Applied Chemistry, Birla Institute of Technology, Mesra, Ranchi, India.
authors.forename: Ashoke
authors.initials: A
authors.lastname: Sharon
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, United States.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr. Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
authors.forename: Sekhar
authors.initials: S
authors.lastname: Chakrabarty
authors.affiliation: Department of Microbiology and Immunology, University of KwaZulu-Natal, 719 Umbilo Road, Durban 4001, South Africa.
authors.forename: Gobardhan
authors.initials: G
authors.lastname: Das
authors.affiliation: National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune, India.
authors.forename: Debashis
authors.initials: D
authors.lastname: Mitra
authors.affiliation: ICMR Virus Unit, ID and BG Hospital, General Block 4, 57 Dr. Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India. Electronic address: debprasadc@yahoo.co.in.
authors.forename: Debprasad
authors.initials: D
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006246:Harmaline / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006561:Herpes Simplex / Q000188:drug therapy / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008807:Mice, Inbred BALB C; D019666:Rubiaceae / Q000737:chemistry; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D006246:Harmaline
keywords: Ethnomedicine; HSV; Immediate-early transcription; LSD1; Ophiorrhiza nicobarica