Anti-Viral Azide Containing Compounds

Abstract

Methods of using azide-modified biomolecules, such as fatty acids, carbohydrates and lipids, to treat a plant, an insect or an animal infected with a virus or to inhibit infectivity of a virus, such as the human immunodeficiency virus, are provided. Also provided are methods of labeling a virus, such as human immunodeficiency virus, with an azide-modified biomolecule, such as a fatty acid, a carbohydrate, or an isoprenoid lipid. Also, provided are methods of tracking a virus in vivo, with an azide-modified biomolecule, such as a fatty acid, a carbohydrate, or an isoprenoid lipid. The azide-modified biomolecules may be combined with a pharmaceutically acceptable excipient to produce a pharmaceutical composition, optionally containing another anti-viral agent and/or a delivery agent, such as a liposome.

1 . A method of producing a virus labeled with an azide-modified fatty acid, an azide-modified carbohydrate, an azide-modified isoprenoid lipid, or a pharmaceutically acceptable salt thereof, the method comprising contacting a cell infected with the virus with the azide-modified fatty acid, the azide-modified carbohydrate, the azide-modified isoprenoid lipid, or pharmaceutically acceptable salt thereof so that the azide-modified fatty acid, the azide-modified carbohydrate, the azide-modified isoprenoid lipid, or pharmaceutically acceptable salt thereof enters the cell and is incorporated into a protein of the virus, thereby producing the labeled virus. 
     
     
         2 . The method of  claim 1 , wherein the azide-modified fatty acid or pharmaceutically acceptable salt thereof, has the formula:
   Y—CH 2 —X—CO 2 H
   
       wherein,
 Y is H or an azido group; and 
 when Y is an azido group, X is a linear or branched carbon chain comprising 6 to 28 carbons, wherein one or more of said carbons may be independently replaced by an oxygen, selenium, silicon, sulfur, SO, SO 2  or NR 1 , or wherein one or more pairs of said carbons adjacent to one another may be attached to one another by a double or triple bond; or 
 when Y is H, X is a linear or branched carbon chain comprising 6 to 28 carbons, wherein one hydrogen on one of said carbons is replaced with an azido group and wherein one or more of said carbons not having an the azido group attached thereto may be independently replaced by an oxygen, selenium, silicon, sulfur, SO, SO 2  or NR 1 , or wherein one or more pairs of said carbons adjacent to one another and not having an azido group may be attached to one another by a double or triple bond; 
 
       wherein, R 1  is H or an alkyl comprising 1 to 6 carbons. 
     
     
         3 . The method of  claim 2 , wherein Y is an azido group. 
     
     
         4 . The method of  claim 3 , wherein X is a linear carbon chain. 
     
     
         5 . The method of  claim 4 , wherein the carbon chain comprises 8 to 15 carbons. 
     
     
         6 . The method of  claim 5 , wherein the carbon chain does not contain an oxygen, selenium, silicon, sulfur, SO, SO 2  or NR 1 . 
     
     
         7 . The method of  claim 6 , wherein the carbon chain does not contain a double or triple bond. 
     
     
         8 . The method of  claim 7 , wherein the azide-modified fatty acid is 15-azidopentadecanoic acid or pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 7 , wherein the azide-modified fatty acid is 12-azidododecanoic acid or pharmaceutically acceptable salt thereof. 
     
     
         10 . The method of  claim 1 , wherein the cell is a human cell. 
     
     
         11 . The method of  claim 1 , wherein the virus is a human immunodeficiency virus. 
     
     
         12 . The method of  claim 1 , wherein the cell is an insect cell. 
     
     
         13 . The method of  claim 1 , wherein the virus is a baculovirus. 
     
     
         14 . The method of  claim 1 , wherein the azide-modified carbohydrate, azide-modified fatty acid, azide-modified isoprenoid lipid, or pharmaceutically acceptable salt is formulated with a pharmaceutically acceptable excipient. 
     
     
         15 . The method of  claim 14 , further comprising the step of administering to the cell the azide-modified carbohydrate, azide-modified fatty acid, azide-modified isoprenoid lipid, or pharmaceutically acceptable salt which is formulated with a pharmaceutically acceptable excipient. 
     
     
         16 . A method of tracking a virus in vivo comprising the steps of
 contacting cultured cells or a subject with an azide-modified carbohydrate, azide-modified fatty acid, azide-modified isoprenoid lipid, or a pharmaceutically acceptable salt thereof;   contacting the cultured cells or the subject with an alkyne labeled reporter molecule; and   tracking the reporter-labeled virus in the cultured cells or the subject.   
     
     
         17 . The method of  claim 16 , wherein the cultured cells or the subject is contacted with an azide-modified fatty acid or pharmaceutically acceptable salt thereof. 
     
     
         18 . The method of  claim 17 , wherein the azide-modified fatty acid or pharmaceutically acceptable salt thereof, has the formula:
   Y—CH 2 —X—CO 2 H
   
       wherein,
 Y is H or an azido group; and 
 when Y is an azido group, X is a linear or branched carbon chain comprising 6 to 28 carbons, wherein one or more of said carbons may be independently replaced by an oxygen, selenium, silicon, sulfur, SO, SO 2  or NR 1 , or wherein one or more pairs of said carbons adjacent to one another may be attached to one another by a double or triple bond; or 
 when Y is H, X is a linear or branched carbon chain comprising 6 to 28 carbons, wherein one hydrogen on one of said carbons is replaced with an azido group and wherein one or more of said carbons not having an the azido group attached thereto may be independently replaced by an oxygen, selenium, silicon, sulfur, SO, SO 2  or NR 1 , or wherein one or more pairs of said carbons adjacent to one another and not having an azido group may be attached to one another by a double or triple bond; 
 
       wherein, R 1  is H or an alkyl comprising 1 to 6 carbons. 
     
     
         19 . The method of  claim 18 , wherein Y is an azido group. 
     
     
         20 . The method of  claim 19 , wherein X is a linear carbon chain. 
     
     
         21 . The method of  claim 20 , wherein the carbon chain comprises 8 to 15 carbons. 
     
     
         22 . The method of  claim 21 , wherein the carbon chain does not contain an oxygen, selenium, silicon, sulfur, SO, SO 2  or NR 1 . 
     
     
         23 . The method of  claim 22 , wherein the carbon chain does not contain a double or triple bond. 
     
     
         24 . The method of  claim 23 , wherein the azide-modified fatty acid is 15-azidopentadecanoic acid or pharmaceutically acceptable salt thereof. 
     
     
         25 . The method of  claim 23 , wherein the azide-modified fatty acid is 12-azidododecanoic acid or pharmaceutically acceptable salt thereof.