Assay and medicament

Abstract

The disclosure relates to defective interfering viruses and defective interfering virus RNAs that are effective as antiviral agents. The disclosure also relates to methods for identifying defective interfering virus RNAs that can be used as effective antiviral agents.

1 . A cloned or recombinant defective interfering (DI) influenza A virus including a modified RNA derived from one of native influenza A virus segments 1, 2 or 3, wherein said modified RNA comprises:
 (a) a length of between 300 to 600 nucleotides;   (b) at least 100 nucleotides from the 5′ and 3′ ends of the one of native influenza A virus segments 1, 2 or 3; and   (c) one or more nucleotide deletions introduced in a central portion of said one of native influenza A virus segments 1, 2, or 3;   whereby said cloned or recombinant DI influenza A virus interferes with RNA production from each of native influenza A virus segments 1, 2 and 3.   
     
     
         2 . The DI influenza A virus according to  claim 1 , wherein the DI influenza A virus is not 1/244. 
     
     
         3 . The DI influenza A virus according to  claim 1 , provided as an antiviral agent for treatment or prophylaxis of influenza A infection. 
     
     
         4 . The DI influenza A virus according to  claim 1 , wherein the modified RNA comprises from about 100 to about 500 contiguous nucleotides from a substantially intact 5′ end of said one of native influenza A virus segments 1, 2, or 3. 
     
     
         5 . The DI influenza A virus according to  claim 1 , wherein the modified RNA comprises from about 100 to about 500 contiguous nucleotides from a substantially intact 3′ end of said one of native influenza A virus segments 1, 2, or 3. 
     
     
         6 . The DI influenza A virus according to  claim 1 , wherein the one or more introduced nucleotide deletions span from about 1000 to about 2000 nucleotides from the central portion of said one of native influenza A virus segments 1, 2, or 3. 
     
     
         7 . A defective interfering virus RNA, wherein the RNA is mutated to prevent expression of any encoded protein. 
     
     
         8 . The DI virus RNA according to  claim 7 , wherein one or more AUG initiation codons are mutated. 
     
     
         9 . The DI virus RNA according to  claim 8 , wherein all AUG initiation codons are mutated. 
     
     
         10 . The DI virus RNA according to  claim 8 , wherein the one or more AUG initiation codons are mutated to AUC. 
     
     
         11 . The DI virus RNA according to  claim 7 , wherein the DI virus is 1/244. 
     
     
         12 . A DI virus which comprises the DI virus RNA according to  claim 7 . 
     
     
         13 . The DI virus according to  claim 12 , formulated as an antiviral agent for treatment or prophylaxis of influenza A infection. 
     
     
         14 . A method for treatment or prophylaxis of influenza A infection, comprising administering an effective amount of a cloned or recombinant defective interfering (DI) influenza A virus including a modified RNA derived from one of native influenza A virus segments 1, 2 or 3, wherein said modified RNA comprises:
 (a) a length of between 300 to 600 nucleotides;   (b) at least 100 nucleotides from the 5′ and 3′ ends of the one of native influenza A virus segments 1, 2 or 3; and   (c) one or more nucleotide deletions introduced in a central portion of said one of native influenza A virus segments 1, 2, or 3;   whereby said cloned or recombinant DI influenza A virus interferes with RNA production from each of native influenza A virus segments 1, 2 and 3.   
     
     
         15 . The method according to  claim 14 , wherein the DI influenza A virus is not 1/244. 
     
     
         16 . The method according to  claim 14 , including providing the modified RNA comprising from about 100 to about 500 contiguous nucleotides from a substantially intact 5′ end of said one of native influenza A virus segments 1, 2, or 3. 
     
     
         17 . The method according to  claim 14 , including providing the modified RNA comprising from about 100 to about 500 contiguous nucleotides from a substantially intact 3′ end of said one of native influenza A virus segments 1, 2, or 3. 
     
     
         18 . The method according to  claim 14 , including providing the modified RNA comprising the one or more introduced nucleotide deletions spanning from about 1000 to about 2000 nucleotides from the central portion of said one of native influenza A virus segments 1, 2, or 3.