RNA Secondary Structure as a First Step for Rational Design of the Oligonucleotides towards Inhibition of Influenza A Virus Replication

• Published in: Pathogens (Basel) Vol. 9; no. 11; p. 925
• Main Authors: Szabat, Marta, Lorent, Dagny, Czapik, Tomasz, Tomaszewska, Maria, Kierzek, Elzbieta, Kierzek, Ryszard
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 07.11.2020; MDPI
• Subjects: Acids; Antigens; Antisense oligonucleotides; Antisense therapy; Antiviral agents; antiviral strategies; Design; Drug development; Drugs; dynamics; Gene expression; genome; Genomes; Glycoproteins; Influenza; Influenza A; Influenza A virus; information; Life cycles; Ligands; microRNA; MicroRNAs; miRNA; Mutation; Nucleic acids; Oligonucleotides; Packaging; pandemic; Pandemics; pathogens; prediction; Protein structure; Proteins; Recombination; Replication; Review; Ribonucleic acid; ribonucleoproteins; RNA; RNA interference; RNA structure; RNA viruses; Secondary structure; Segments; siRNA; small interfering RNA; structure-activity relationships; Structure-function relationships; Therapeutic targets; Transcription; Vaccination; Viral infections; virion; Virions; virus replication; Viruses
• ISSN: 2076-0817; 2076-0817
• DOI: 10.3390/pathogens9110925

Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA—vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field.