Sequence-specific cleavage of BM2 gene transcript of influenza B virus by 10-23 catalytic motif containing DNA enzymes significantly inhibits viral RNA translation and replication.

Abstract

One of the hallmarks of progression of influenza virus replication is the step involving the virus uncoating that occurs in the host cytoplasm. The BM2 ion channel protein of influenza B virus is highly conserved and is essentially required during the uncoating processes of virus, thus an attractive target for designing antiviral drugs. We screened several DNA enzymes (Dzs) containing the 10-23 catalytic motif against the influenza B virus BM2 RNA. Dzs directed against the predicted single-stranded bulge regions showed sequence-specific cleavage activities. The Dz209 not only showed significant intracellular reduction of BM2 gene expression in transient-expression system but also provided considerable protection against influenza B virus challenge in MDCK cells. Our findings suggest that the Dz molecule can be used as selective and effective inhibitor of viral RNA replication, and can be explored further for development of a potent therapeutic agent against influenza B virus infection.

• Authors: Binod Kumar, Prashant Kumar, Roopali Rajput, Latika Saxena, Mradul K Daga, Madhu Khanna
• Journal: Nucleic acid therapeutics (Nucleic Acid Ther) Vol. 23 Issue 5 Pg. 355-62 (Oct 2013) ISSN: 2159-3345 [Electronic] United States
• PMID: 23971908 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• BM2 polypeptide, influenza B virus
• DNA, Catalytic
• RNA, Messenger
• RNA, Viral
• Viral Proteins

Topics

• Animals
• Antiviral Agents (chemical synthesis, metabolism)
• Catalytic Domain
• DNA, Catalytic (chemical synthesis, metabolism)
• Dogs
• Influenza B virus (genetics, growth & development, metabolism)
• Madin Darby Canine Kidney Cells
• Molecular Sequence Data
• Nucleotide Motifs
• RNA Cleavage
• RNA, Messenger (chemistry, genetics, metabolism)
• RNA, Viral (chemistry, genetics, metabolism)
• Viral Proteins (chemistry, genetics, metabolism)
• Virus Replication