Preventing or treating viral infection using an inhibitor of the LSD1 protein, a MAO inhibitor or an inhibitor of LSD1 and a MAO inhibitor
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8916596-B2
Publication Date
2014-12-23
Expiration Date
2029-07-23
Abstract
An embodiment of the invention provides preventing or treating a viral infection of a host, comprising administering to the host an effective amount of an inhibitor of the protein LSD1 and/or a monoamine oxidase inhibitor. Another embodiment of the invention provides preventing or treating reactivation of a virus after latency in a host, comprising administering to the host an effective amount of an inhibitor of the protein LSD1 and/or a monoamine oxidase inhibitor. Another embodiment of the invention provides preventing or treating a viral infection in a mammal that has undergone, is undergoing, or will undergo an organ or tissue transplant, comprising administering to the mammal an effective amount of an inhibitor of the protein LSD1 and/or a monoamine oxidase inhibitor before, during, and/or after the organ or tissue transplant. The viral infection may be due to a herpesvirus, such as herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), varicella zoster virus (VZV), or cytomegalovirus (CMV). The viral infection may also be due to an adenovirus, including types 1-5.
Core Innovation
The invention provides methods of preventing or treating viral infections by administering to a host an effective amount of an inhibitor of the protein LSD1 and/or a monoamine oxidase inhibitor (MAOI). It also includes methods for preventing or treating reactivation of a virus after latency in a host by administering these inhibitors. Additionally, the invention covers treating viral infections in mammals undergoing organ or tissue transplants using these inhibitors before, during, and/or after transplantation.
The viral infections addressed include those caused by herpesviruses such as herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and adenoviruses including types 1-5. The inhibitors target LSD1, a histone demethylase involved in viral immediate early gene transcription, and MAOIs that inhibit LSD1's demethylase activity. LSD1's role in modulating chromatin marks regulates the progression of viral lytic infection and latency reactivation cycles.
The background highlights a problem: viruses rely upon host cell transcriptional machinery, and methylation of chromatin influences viral gene expression and infection progression. A need exists for methods to prevent or treat viral infections effectively considering this chromatin modulation mechanism.
Claims Coverage
The claims define three independent inventive features related to methods of treating viral infections or reactivations using LSD1 inhibitors, specifically monoamine oxidase inhibitors, involving detection of viral immediate early gene expression.
Method of treating viral infection by administering LSD1 inhibitor
A method for treating a herpesvirus or adenovirus infection in a host by detecting immediate early gene expression of the viral infection, administering an effective amount of an LSD1 inhibitor that is a monoamine oxidase inhibitor, and detecting reduced IE gene expression post administration, wherein treatment is confirmed by lower IE gene expression.
Method of treating viral reactivation after latency using LSD1 inhibitor
A method of treating reactivation of herpesvirus or adenovirus after latency in a host by detecting viral immediate early gene expression, administering an effective amount of an LSD1 inhibitor that is a monoamine oxidase inhibitor, and determining treatment success by reduced IE gene expression levels after the inhibitor's administration.
Method of treating viral infection in organ or tissue transplant recipients
A method of treating herpesvirus or adenovirus infection in mammals undergoing organ or tissue transplant by detecting viral immediate early gene expression, administering an effective amount of an LSD1 inhibitor that is a monoamine oxidase inhibitor before, during, and/or after transplant, and confirming treatment through decreased IE gene expression after administration.
The independent claims cover methods for treating viral infections or reactivations through detecting viral IE gene expression and administering LSD1 inhibitors that are monoamine oxidase inhibitors, with various embodiments including treatment of transplant recipients and administration routes.
Stated Advantages
Inhibiting LSD1 with MAOIs results in dose-dependent decreases in viral mRNA and immediate early proteins, reducing viral replication without significant cellular toxicity.
Treatment with inhibitors prevents or reduces viral reactivation from latency, demonstrated by significant reductions in viral yields in infected mouse models.
Use of LSD1 inhibitors allows preservation of transplanted organs or tissues containing latent virus without the need to destroy them, enabling life-saving transplants despite potential viral presence.
Documented Applications
Treatment and prevention of viral infections caused by herpesviruses (HSV-1, HSV-2, VZV, CMV) and adenoviruses (Types 1-5) in hosts.
Inhibition of reactivation of herpesvirus infections after latency, particularly HSV-1.
Therapeutic application for mammals undergoing organ or tissue transplantation to prevent or treat latent or active viral infections associated with the transplant.
Topical treatment formulations (creams or lotions) for clearance of cold sores, genital sores, and shingles caused by herpesviruses.
Interested in licensing this patent?