Broad antiviral therapy with membrane modifying oxysterols

Abstract

This invention relates, e.g., to a method for inhibiting the growth and/or proliferation and/or infectivity of a virus in a cell, such as a mammalian cell (e.g. for inhibiting entry of the virus into the cell), comprising administering, or causing to be administered, to the cell, 25-hydroxycholesterol (25HC) in an amount sufficient to inhibit the growth and/or proliferation and/or infectivity of the virus in the cell. The method can be carried out in vivo or in vitro. Among the viruses that can be inhibited are, e.g., VSV, HSV, MHV68, HCV, HIV, EBOV, RVFV, RSSEV and Nipah virus. In one embodiment of the invention, the 25HC is administered topically, e.g. to a mucosal surface.

1 . A method for inhibiting the growth and/or proliferation and/or infectivity of a virus in a cell, comprising administering, or causing to be administered, to the cell, 25-hydroxycholesterol (25HC) in an amount sufficient to inhibit the growth and/or proliferation and/or infectivity of the virus in the cell,
 wherein, if the cell is in vitro, the 25HC is administered to the cell, and the virus is vesicular stomatitis virus (VSV), herpes simplex virus (HSV), murine gammaherpes virus (MHV68), hepatitis C virus (HCV), Ebola virus (EBOV), or Nipah virus; and   wherein, if the cell is in a subject, the 25HC is administered or caused to be administered to the subject, and the virus is vesicular stomatitis virus (VSV), herpes simplex virus (HSV), murine gammaherpes virus (MHV68), hepatitis C virus (HCV), human-immunodeficiency virus (HIV), Ebola virus (EBOV), or Nipah virus.   
     
     
         2 . The method of  claim 1 , wherein the method is a method for preventing a viral infection of a mammalian cell in vitro, and the method comprises administering to the mammalian cell 25HC in an amount sufficient to inhibit infectivity of the virus in the cell. 
     
     
         3 . The method of  claim 1 , wherein the method is a method for preventing a viral infection of a mammal, and the method comprises administering, or causing to be administered, to the mammal, 25HC in an amount sufficient to inhibit infectivity of the virus in the mammal. 
     
     
         4 . The method of  claim 1 , wherein the method is a method for inhibiting entry of the virus into a mammalian cell in vitro, and the method comprises contacting the mammalian cell with 25HC in an amount sufficient to inhibit entry of the virus into the cell. 
     
     
         5 . The method of  claim 1 , wherein the method is a method for inhibiting entry of the virus into a cell in a mammalian subject, and the method comprises administering, or causing to be administered, to the mammal, 25HC in an amount sufficient to inhibit entry of the virus into the cell. 
     
     
         6 . The method of  claim 3 , wherein said 25HC is administered by a route selected from the group consisting of topical administration, oral administration, nasal administration, rectal administration, vaginal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, inhalation administration, and intramuscular injection. 
     
     
         7 . The method of  claim 3 , wherein the 25HC is administered topically, vaginally, rectally, or to the buccal cavity. 
     
     
         8 . The method of  claim 3 , wherein the 25HC is s administered to a mucosal surface. 
     
     
         9 . The method of  claim 3 , wherein the 25HC is formulated as a cream, gel, or foam for rectal delivery or vaginal delivery or topical administration. 
     
     
         10 . The method of  claim 3 , wherein the 25HC is formulated as a mouthwash for delivery to the buccal cavity. 
     
     
         11 . The method of  claim 3 , wherein the 25HC is formulated for oral or intravenous delivery. 
     
     
         12 . The method of  claim 11 , wherein the 25HC is solubilized in (2-hydroxy)-beta-cyclodextrin. 
     
     
         13 . The method of  claim 2 , wherein the mammalian cell is from a non-human mammal. 
     
     
         14 . The method of  claim 2 , wherein the mammalian cell is human. 
     
     
         15 . The method of  claim 14 , wherein the human is identified as being at risk for an infection by the virus. 
     
     
         16 . The method of  claim 14 , wherein the human is identified as having an infection by the virus. 
     
     
         17 . A method for identifying putative inhibitors of viral entry into cells which exhibit lower levels of side effects than does 25HC, comprising testing analogs of 25HC in vitro for their ability to
 a) exhibit anti-viral activity,   b) exhibit lower levels of cell cytoxicity than does 25HC, and   c) inhibit lipid metabolism to a lower level than does 25HC.   
     
     
         18 . The method of  claim 1 , which is a method for inhibiting the growth and/or proliferation and/or infectivity of a virus in a cell.