A new class of antivirals: antisense oligonucleotides combined with a hydrophobic substituent effectively inhibit influenza virus reproduction and synthesis of virus-specific proteins in MDCK cells

• Published in: FEBS letters Vol. 259; no. 2; pp. 327 - 330
• Main Authors: Kabanov, Alexander V., Vinogradov, Sergei V., Ovcharenko, Alexander V., Krivonos, Alexander V., Melik-Nubarov, Nikolai S., Kiselev, Vsevolod I., Severin, Eugenii S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 1990; Elsevier
• Subjects: Aerosol OT, sodium bis(2-ethylhexyl)sulfosuccinate; Analytical, structural and metabolic biochemistry; Animals; Antisense; Antiviral Agents - pharmacology; Biological and medical sciences; Cell Line; Dogs; Fundamental and applied biological sciences. Psychology; Hepes, N(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid sodium salt; Influenza; influenza A virus; Influenza A virus - drug effects; Influenza A virus - physiology; Inhibition; Kidney; Mes, 2-(N-morpholino)ethanesulfonic acid; Molecular Weight; Nucleic acids; Nucleic bases, nucleotides; Oligonucleotide; Oligoribonucleotides - chemical synthesis; Oligoribonucleotides - pharmacology; PFU, plaque forming units; RNA - chemical synthesis; RNA - pharmacology; RNA, Antisense; RNA, Messenger - antagonists & inhibitors; Translation; Viral Proteins - antagonists & inhibitors; Viral Proteins - biosynthesis; Viral Proteins - isolation & purification; Virus; Virus Replication - drug effects; Virus; Mes, 2-( N-morpholino)ethanesulfonic acid; Translation; PFU, plaque forming units; Influenza; Antisense; Oligonucleotide; Inhibition; Aerosol OT, sodium bis(2-ethylhexyl)sulfosuccinate; Hepes, N(2-hydroxyethyl)piperazine- N'-2-ethanesulfonic acid sodium salt; Fissipedia; Cell culture; Carnivora; Orthomyxoviridae; Influenzavirus; Kidney; Proteins; Vertebrata; Mammalia; Cell line; Antiviral; Epithelial cell; Infected cell; Dog
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(90)80039-L

To enhance the penetration of oligonucleotide (‘oligo’) into cells, the oligo was combined with the hydrophobic undecyl residue. Using the ‘DNA-synthesator’, we synthesized oligo, complementary to the loop-forming site of the RNA, encoding polymerase 3 of the influenza virus (type A), and combined it with the undecyl residue added to the 5' terminal phosphate group. It was found that the modified oligo effectively suppresses the influenza A/PR8/34 (H1N1) virus reproduction and inhibits the synthesis of virus-specific proteins in MDCK cells. Under the same conditions, the non-modified antisense oligo and modified nonsense oligo did not affect the virus development.