Hydrophobized antiviral antibodies and antisense oligonucleotides.
A method of suppressing virus reproduction in cells has been proposed. The approach consists of affecting the cells with antiviral antibodies artificially hydrophobized with fatty acid residues. Reproduction of influenza viruses in MDCK cells and respiratory-synticial virus in HeLa cells was used as a model to demonstrate that poly- and monoclonal antibodies, modified by 1 or 2 stearic acid residues, are potent, unlike the non-modified antibodies, at inhibiting viral reproduction. The observed phenomenon is apparently due to penetration of hydrophobized antibodies into the cells. Thus, in particular, considerable antiviral activity is exhibited by monoclonal antibodies against NP-protein of influenza virus, which is an antigen accessible to antibodies only inside the infected cells. Hydrophobized antibodies do not affect the kinetics of viral protein synthesis; they block the virus withdrawal from the cells, probably by interfering with the assembling and budding of virus particles. To enhance penetration of oligonucleotides ("oligos") into cells, chemical modification of the former at the 5'-end phosphate group by fatty radicals has been suggested. The undecanol-modified oligo namely an oligo complementary to the protein binding sites located at the influenza virus polymerases encoding RNA, was synthesized using a DNA-synthesator. The above modified oligo effectively suppressed the influenza A/PR8/34 virus reproduction and inhibited synthesis of the virus-specific proteins in MDCK cells. The non-modified antisense oligo and the modified nonsense oligo did not affect the virus development under the same conditions.
Severin
E S
ES
Research Center of Molecular Diagnostics, USSR Ministry of Health, Moscow.
Melik-Nubarov
N S
NS
Ovcharenko
A V
AV
Vinogradov
S V
SV
Kiselev
V I
VI
Kabanov
A V
AV
D000818:Animals; D000914:Antibodies, Viral / Q000494:pharmacology*; D000998:Antiviral Agents; D001483:Base Sequence; D002460:Cell Line; D002642:Chick Embryo; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009975:Orthomyxoviridae / Q000187:drug effects / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects*
D000914:Antibodies, Viral; D000998:Antiviral Agents; D016376:Oligonucleotides, Antisense; D012367:RNA, Viral