Bleomycin-Fe(II) agent with potentiality for treating drug-resistant H1N1 influenza virus: A study using electrochemical RNA beacons

Abstract

Rapid emergence of new strains of drug-resistant H1N1 influenza viruses calls for effective drugs for the controls prior to their outbreaks. In the present work, electrochemical H1N1 RNA beacons have been newly designed for exploring the potentiality of an anticancer agent of Bleomycin (BLM) with Fe (ΙΙ) ions (BLM-Fe(ΙΙ)) alternatively the treatment of drug-resistant H1N1 strains with H274Y gene mutation. Herein, biotinylated (−) ssRNA of H1N1 virus and its complementary (+) ssRNA were labeled with electrochemical signal probes of ferrocene and anthraquinone, respectively. The resultants were hybridized and conjugated with avidin-modified magnetic beads to create electrochemical RNA beacons. The electrochemical signal variation of the H1N1 RNA beacon treated with the RNA degradation agent of BLM-Fe(ΙΙ) were monitored. Results indicate that the BLM-Fe(ΙΙ) agent could effectively cleave both H1N1 dsRNAs and ssRNAs at selective cutting sites, as evidenced by the mass spectrometry analysis. This indicates that the BLM-Fe(II) agent could be utilized to block the viral-host infection process by curbing the host-cell viral RNA-mRNA transcription or inactivate the viruses through the cleavage of viral genomes. The efficiency of the BLM-Fe(ΙΙ) agent was verified with clinical seasonal H1N1 samples using real-time polymerase chain reaction. The therapeutic gene drug of BLM-Fe(ΙΙ) holds great potential for controlling new strains of H1N1 virus resistant to clinical antiviral drugs. More importantly, the so designed RNA beacons may provide a rapid, sensitive and cost-effective platform of drug screening by monitoring the drug-DNA/RNA interactions.