Methods and compounds to inhibit enveloped virus release

Abstract

A compound having an antiviral activity for inhibiting release of an enveloped virus from a cell is disclosed, including methods of inhibiting release of an enveloped virus from a cell. The antiviral activity of the compound includes inhibiting formation of an associative complex or disrupting formation of an associative complex. The associative complex comprises an L-domain motif of the enveloped virus and at least one cellular polypeptide, or fragment thereof, capable of binding the L-domain motif of the enveloped virus.

What is claimed: 
     
         1 . A compound having an antiviral activity for inhibiting release of an enveloped virus from a cell. 
     
     
         2 . The compound of  claim 1 , wherein the antiviral activity comprises:
 (i) inhibiting formation of an associative complex; or   (ii) disrupting formation of an associative complex,   wherein the associative complex comprises an L-domain motif of the enveloped virus and at least one cellular polypeptide, or fragment thereof, capable of binding the L-domain motif of the enveloped virus.   
     
     
         3 . The compound of  claim 2 , wherein L-domain motif comprises at least one of a PY-motif or a PTAP-motif. 
     
     
         4 . The compound of  claim 2 , wherein L-domain motif comprises at least one member selected from the group consisting of SEQ ID NOS:1-22. 
     
     
         5 . The compound of  claim 2 , wherein the at least one cellular polypeptide comprises an ESCRT component protein. 
     
     
         6 . The compound of  claim 5 , wherein the ESCRT component protein comprises at least one member selected from a Nedd 4-related family peptide and TSG101, fragments thereof, and combinations thereof. 
     
     
         7 . The compound of  claim 6 , wherein ESCRT component protein comprises one of SEQ ID NOS: 24, 29, 32 and 33. 
     
     
         8 . The compound of  claim 1 , wherein the enveloped virus comprises at least one member selected from the group consisting of Lassa fever virus, lymphocytic choriomeningitis virus, Ebola virus, Marberg virus, hepatitis B virus, Herpes simplex virus, type 1, Herpes simplex virus, type 2, cytomegalovirus, Simian virus, type 5, Mumps virus, avian sarcoma leucosis virus, human immunodeficiency virus, type 1, human T-lymphotrophic virus, type 1, equine infectious anemia virus, vesicular stomatitis virus, rabies virus and combinations thereof. 
     
     
         9 . The compound of  claim 1 , wherein the cell comprises a host cell for supporting active replication of the enveloped virus. 
     
     
         10 . The compound of  claim 1 , wherein the compound comprises at least one member selected from the group consisting of compounds having the structure of formulas (VII-(XIII): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and combinations thereof. 
     
     
         11 . A method of inhibiting release of an enveloped virus from a cell, comprising contacting the cell with a compound having an antiviral activity, said antiviral activity comprises:
 (i) inhibiting formation of an associative complex; or   (ii) disrupting formation of an associative complex,   wherein the associative complex comprises an L-domain motif of the enveloped virus and at least one cellular polypeptide, or fragment thereof, capable of binding the L-domain motif of the enveloped virus.   
     
     
         12 . The method of  claim 11 , wherein L-domain motif comprises at least one of a PY-motif or a PTAP-motif. 
     
     
         13 . The method of  claim 11 , wherein L-domain motif comprises at least one member selected from the group consisting of SEQ ID NOS:1-22. 
     
     
         14 . The method of  claim 11 , wherein the at least one cellular polypeptide comprises an ESCRT complex protein. 
     
     
         15 . The method of  claim 14 , wherein the ESCRT component protein comprises at least one member selected from a Nedd 4-related family peptide and TSG101, fragments thereof, and combinations thereof. 
     
     
         16 . The method of  claim 14 , wherein ESCRT component protein comprises one of SEQ ID NOS: 24, 29, 32 and 33. 
     
     
         17 . The method of  claim 11 , wherein the enveloped virus comprises at least one member selected from the group consisting of Lassa fever virus, lymphocytic choriomeningitis virus, Ebola virus, Marberg virus, hepatitis B virus, Herpes simplex virus, type 1, Herpes simplex virus, type 2, cytomegalovirus, Simian virus, type 5, Mumps virus, avian sarcoma leucosis virus, human immunodeficiency virus, type 1, human T-lymphotrophic virus, type 1, equine infectious anemia virus, vesicular stomatitis virus, rabies virus and combinations thereof. 
     
     
         18 . The method of  claim 11 , wherein the cell comprises a host cell for supporting active replication of the enveloped virus. 
     
     
         19 . The method of  claim 11 , wherein the compound comprises at least one member selected from the group consisting of compounds having the structure of formulas (VII)-(XIII): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and combinations thereof. 
     
     
         20 . A pharmaceutical composition comprising a compound having an antiviral activity for inhibiting release of an enveloped virus from a cell and optionally a pharmaceutically acceptable carrier.