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.
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.
Kabanov
A V
AV
Research Center of Molecular Diagnostics, USSR Ministry of Health, Moscow.
Vinogradov
S V
SV
Ovcharenko
A V
AV
Krivonos
A V
AV
Melik-Nubarov
N S
NS
Kiselev
V I
VI
Severin
E S
ES
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D009980:Influenza A virus / Q000187:drug effects / Q000502:physiology*; D007668:Kidney; D008970:Molecular Weight; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D012313:RNA / Q000138:chemical synthesis / Q000494:pharmacology*; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D009843:Oligoribonucleotides; D016372:RNA, Antisense; D012333:RNA, Messenger; D014764:Viral Proteins; D012313:RNA