Human hepatitis B and immunodeficiency viruses 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 human immunodeficiency, hepatitis C, varicella-zoster and cytomegalo-viruses.
METHODS:
The in vitro inhibitory action of RTZ on HIV-1 strain LAI, human hepatitis B virus 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 the bloodborne human hepatitis B virus 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 the bloodborne human hepatitis C and Ebola Zaire viruses 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 hepatitis B and immunodeficiency viruses.
CONCLUSIONS:
RTZ represents the first reported antiviral agent capable of eradicating human immunodeficiency and hepatitis B 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.
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