Antiviral activity of influenza virus M1 zinc finger peptides.
Matrix protein (M1) of influenza virus inhibits its own polymerase; this suggested that a peptide segment of M1 with inhibitory properties could serve as an antiviral agent. A peptide synthesized to the Zn2+ finger region of the M1 sequence of influenza virus strain A/PR/8/34 centered around amino acids residues 148 to 166 was shown earlier to be 1,000-fold more effective as a polymerase inhibitor than M1. This peptide, designated peptide 6, represents a Zn2+ finger which includes a 7-residue "loop" and a 4-residue "tail" in addition to the 4 residues on either side of the loop involved in coordination of Zn2+. We have now demonstrated antiviral activity for this peptide in microassays measuring inhibition of the viral cytopathic effect. When the peptide was introduced into tissue culture 5 min after viral challenge with A/PR/8/34, antiviral activity was seen at levels as low as 0.1 nM; on a molar basis, the peptide was shown to be 1,000- to 2,500-fold more effective than ribavirin or amantadine. Antiviral activity was seen with addition of the peptide up to 1 h after viral infection; however, little or no activity was seen at later times, suggesting that viral replication is inhibited at an early stage, possibly at the level of transcription. Reduction in the finger loop or tail length reduced antiviral activity; reduction in the number of residues involved in coordination of Zn2+ abolished antiviral activity. In addition to A/PR/8/34, peptide 6 was shown to have antiviral activity against other type A influenza viruses, including those representing H1N1, H2N2, and H3N2 subtypes. Antiviral activity against type B influenza viruses was also seen. A low level of activity against vesicular stomatitis virus was observed. Zn2+ finger peptides or analogs of Zn2+ finger peptides may provide a new class of antiviral agents effective against influenza virus and possibly other viruses.
Nasser
E H
EH
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595, USA.
Judd
A K
AK
Sanchez
A
A
Anastasiou
D
D
Bucher
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D009981:Influenza B virus / Q000187:drug effects*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D016335:Zinc Fingers
D000998:Antiviral Agents; C031540:M-protein, influenza virus; C488936:M1 protein, Influenza A virus; D010455:Peptides; D014763:Viral Matrix Proteins