title: Retinazone inhibits certain blood-borne human viruses including Ebola virus Zaire.
abstract: BACKGROUND
  Human HBV and HIV integrate their retro-transcribed DNA proviruses into the human host genome. Existing antiretroviral drug regimens fail to directly target these intrachromosomal xenogenomes, leading to persistence of viral genetic information. Retinazone (RTZ) constitutes a novel vitamin A-derived (retinoid) thiosemicarbazone derivative with broad-spectrum antiviral activity versus HIV, HCV, varicella-zoster virus and cytomegalovirus.
  
  
  METHODS
  The in vitro inhibitory action of RTZ on HIV-1 strain LAI, human HBV strain ayw, HCV-1b strain Con1, enhanced green fluorescent protein-expressing Ebola virus Zaire 1976 strain Mayinga, wild-type Ebola virus Zaire 1976 strain Mayinga, human herpesvirus 6B and Kaposi's sarcoma-associated herpesvirus replication was investigated. The binding of RTZ to human glucocorticoid receptor was determined.
  
  
  RESULTS
  RTZ inhibits blood-borne human HBV multiplication in vitro by covalent inactivation of intragenic and intraexonic viral glucocorticoid response elements, and, in close analogy, RTZ suppresses HIV-1 multiplication in vitro. RTZ disrupts the multiplication of blood-borne human HCV and Ebola Zaire virus at nanomolar concentrations in vitro. RTZ has the capacity to bind to human glucocorticoid receptor, to selectively and covalently bind to intraexonic viral glucocorticoid response elements, and thereby to inactivate human genome-integrated proviral DNA of human HBV and HIV.
  
  
  CONCLUSIONS
  RTZ represents the first reported antiviral agent capable of eradicating HIV and HBV proviruses from their human host. Furthermore, RTZ represents a potent and efficacious small-molecule in vitro inhibitor of Ebola virus Zaire 1976 strain Mayinga replication.
authors: Chammünsterstr. 47, Munich, Germany. andreas.kesel@gmx.de.
authors: Andreas J
authors: AJ
authors: Kesel
authors: Zhuhui
authors: Z
authors: Huang
authors: Michael G
authors: MG
authors: Murray
authors: Mark N
authors: MN
authors: Prichard
authors: Laura
authors: L
authors: Caboni
authors: Daniel K
authors: DK
authors: Nevin
authors: Darren
authors: D
authors: Fayne
authors: David G
authors: DG
authors: Lloyd
authors: Mervi A
authors: MA
authors: Detorio
authors: Raymond F
authors: RF
authors: Schinazi
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D029043:Ebolavirus / Q000145:classification / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology*; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D013882:Thiosemicarbazones; C000594939:retinazone; D014801:Vitamin A
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