ANTIVIRAL ACTIVITY OF INFLUENZA-VIRUS M1 ZINC-FINGER PEPTIDES

Matrix protein (M1) of influenza virus inhibits its own polymerase; th is suggested that a peptide segment of M1 with inhibitory properties c ould serve as an antiviral agent, A peptide synthesized to the Zn2+ fi nger region of the M1 sequence of influenza virus strain A/PR/8/34 cen tered around amino acids residues 148 to 166 was shown earlier to be 1 ,000-fold more effective as a polymerase inhibitor than M1, This pepti de, designated peptide 6, represents a Zn2+ finger which includes a 7- residue ''loop'' and a 4-residue ''tail'' in addition to the 4 residue s on either side of the loop involved in coordination of Zn2+, We have now demonstrated antiviral activity for this peptide in microassays m easuring inhibition of the viral cytopathic effect, When the peptide w as introduced into tissue culture 5 min after viral challenge with A/P R/8/34, antiviral activity was seen at levels as low as 0.1 nM; on a m olar basis, the peptide was shown to be 1,000- to 2,500-fold more effe ctive than ribavirin or amantadine. Antiviral activity was seen with a ddition of the peptide up to 1 h after viral infection; however, littl e or no activity was seen at later times, suggesting that viral replic ation is inhibited at an early stage, possibly at the level of transcr iption, 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, pepti de 6 was shown to have antiviral activity against other type A influen za 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.