Sirtuin modulators as inhibitors of cytomegalovirus

Abstract

Agents and methods of inhibiting or improving the growth of viruses are provided.

1 . A method of inhibiting virus production comprising contacting a virus-infected cell with one or more inhibitors of two or more sirtuins, wherein the sirtuins are selected from SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7. 
     
     
         2 .- 10 . (canceled) 
     
     
         11 . A method of inhibiting virus production comprising contacting a virus-infected cell with a SIRT1 inhibitor and a SIRT2 inhibitor. 
     
     
         12 . The method of  claim 11 , wherein the SIRT1 inhibitor and the SIRT2 inhibitor are a dual SIRT1/SIRT2 inhibitor. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 12 , wherein the dual SIRT1/SIRT2 inhibitor is cambinol, salermide, tenovin-6, tenovin-1, or a combination thereof. 
     
     
         15 .- 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the virus is HCMV, human papilloma virus, HSV1, FluA, adenovirus, influenza virus, hepatitis B virus, hepatitis C virus, or HIV. 
     
     
         22 . The method of  claim 11 , wherein the virus is Adenoviridae; Hepadnaviridae; Herpesviridae; Flaviviridae; Orthomixoviridae; Papillomaviridae; Polyomaviridae; or Retroviridae. 
     
     
         23 . The method of  claim 11 , further comprising contacting the cell with one or more of a SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7 agonist. 
     
     
         24 . (canceled) 
     
     
         25 . The method of  claim 1 , further comprising contacting the virus with a second agent. 
     
     
         26 . The method of  claim 25 , wherein the second agent is an antiviral agent. 
     
     
         27 .- 28 . (canceled) 
     
     
         29 . The method of  claim 1 , wherein the cell is a tumor cell. 
     
     
         30 . The method of  claim 29 , wherein the tumor cell is infected with HCMV. 
     
     
         31 . The method of  claim 1 , wherein the two or more sirtuins are inhibited by inhibiting gene expression of at least one of the two or more sirtuins. 
     
     
         32 .- 36 . (canceled) 
     
     
         37 . The method of  claim 1 , wherein the contacting is in vitro. 
     
     
         38 . The method of  claim 1 , wherein the contacting is in vivo. 
     
     
         39 .- 46 . (canceled) 
     
     
         47 . A method of increasing virus production comprising inhibiting sirtuin gene expression in a virus-infected cell. 
     
     
         48 .- 54 . (canceled) 
     
     
         55 . The method of  claim 47 , wherein the sirtuin gene expression is inhibited by contacting the cell with a dominant negative sirtuin gene, coding sequence or protein. 
     
     
         56 . The method of  claim 47 , wherein the sirtuin gene expression is inhibited in cells from a transgenic animal. 
     
     
         57 . The method of  claim 47 , wherein the sirtuin gene expression is inhibited by mutational inactivation within cultured cells.