Pan-genotypic agents against influenza virus and methods of using the same
Methods of inhibiting influenza A virus in a sample are provided. Aspects of the methods include contacting a sample comprising viral RNA (vRNA) having a PSL2 motif with an effective amount of an agent that specifically binds the PSL2 motif to inhibit the influenza A virus. Also provided are methods of treating or preventing influenza A virus infection in a subject. Also provided are methods for screening a candidate agent for the ability to inhibit influenza A virus in a cell, the method comprising: contacting a sample with a candidate agent; and determining whether the candidate agent specifically binds to the PSL2 motif of vRNA. Also provided are compounds and pharmaceutical compositions comprising an oligonucleotide sequence complementary to a PB2 vRNA region that find use in the subject methods.
1 . A composition comprising: an antiviral oligonucleotide compound or salt thereof, comprising an oligonucleotide sequence 5′ CGACCAAAAGAATTC 3′ (SEQ ID NO:56).
2 . The composition of claim 1 , wherein the oligonucleotide comprises an internucleoside linkage selected from: phosphorothioate, phosphorodithioate, phosphoramidate and thiophosphoramidate linkages.
3 . The composition of claim 2 , wherein the oligonucleotide comprises one or more chiral internucleoside linkages.
4 . The composition of claim 1 , wherein the oligonucleotide comprises one or more 2′-modified nucleotides.
5 . The composition of claim 1 , wherein the oligonucleotide comprises at least 5 deoxyribonucleotide units and is capable of recruiting an RNase.
6 . A composition comprising: an antiviral oligonucleotide compound or salt thereof, comprising an oligonucleotide sequence LNA14: 5′CGACcaaaagaATTC 3′ (SEQ ID NO:81), wherein capitalized letters denote LNA nucleotides and lowercase letters denote DNA nucleotides.
7 . The composition of claim 6 , wherein the oligonucleotide comprises an internucleoside linkage selected from: phosphorothioate, phosphorodithioate, phosphoramidate and thiophosphoramidate linkages.
8 . The composition of claim 7 , wherein the oligonucleotide comprises one or more chiral internucleoside linkages.
9 . A method of treating or preventing a virus infection in a subject, the method comprising:
administering to a subject in need thereof a pharmaceutical composition comprising an effective amount of the composition according to claim 1 .
10 . The method of claim 9 , wherein the subject is at risk of influenza A virus infection and the administering protects the subject against infection for 1 week or more.
11 . The method of claim 9 , wherein the administering comprises weekly, biweekly, or monthly administration of an effective dose of the oligonucleotide compound.
12 . The method of claim 9 , wherein the pharmaceutical composition further comprises an additional active agent selected from a second oligonucleotide active agent and an antiviral drug.
13 . The method of claim 9 , wherein the subject has been diagnosed with or is suspected of having an influenza A virus infection.
14 . A method of treating or preventing a virus infection in a subject, the method comprising:
administering to a subject in need thereof a pharmaceutical composition comprising an effective amount of the composition according to claim 6 .
15 . The method of claim 14 , wherein the subject is at risk of influenza A virus infection and the administering protects the subject against infection for 1 week or more.
16 . The method of claim 14 , wherein the administering comprises weekly, biweekly, or monthly administration of an effective dose of the oligonucleotide compound.
17 . The method of claim 14 , wherein the pharmaceutical composition further comprises an additional active agent selected from a second oligonucleotide active agent and an antiviral drug.
18 . The method of claim 14 , wherein the subject has been diagnosed with or is suspected of having an influenza A virus infection.