The United States of America, as Represented by the Secretary, Department of Health and Human Services

Thomas Kristie

Yu Liang

Jodi Vogel

Anton Simeonov

David Joseph Maloney

Ajit Jadhav

Ganesha Rai Bantukallu

An embodiment of the invention provides a method of 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 a method of 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 a method of 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.

Preventing or treating viral infection using an inhibitor of the LSD1 protein, a MAO inhibitor or an inhibitor of LSD1 and a MAO inhibitor

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.

Disclosed are compounds and pharmaceutical compositions containing compounds that inhibit JMJD2 proteins, including those of the formula (I): wherein R, R, R, R, and Rare as defined herein or pharmaceutically acceptable salts thereof. Also disclosed is a method of preventing or treating a viral infection of a host, comprising administering to the host an effective amount of an inhibitor of the JMJD2 family of histone demethylases, for example, a compound of the formula (I). The viral infection may be a primary infection, reactivation of a virus after latency in a host, or may be in a mammal that has undergone, is undergoing, or will undergo immunosuppressive therapy.

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Silver Spring, MD, United States of America

Thomas Kristie