IN-VIVO ANTIINFLUENZA VIRUS ACTIVITY OF A ZINC-FINGER PEPTIDE

Matrix protein (MI) is a major structural protein of influenza virus, and it inhibits its own polymerase, A 19-amino-acid peptide, correspon ding to a zinc finger region of the M1 sequence of influenza virus str ain A/PR/8/34 (HIN1), centered around amino acids 148 to 166, was synt hesized, This peptide, designated peptide 6, represents a zinc finger which includes a 7-amino-acid loop or finger and a 4-amino-acid tail a t the carboxyl terminus, in addition to the 8 amino acids involved in the coordination of Zn, Three experiments were run to evaluate the act ivity of peptide 6 on infections induced in mice by influenza A/PR/8/3 4 and A/Victoria/3/75 (H3N2) viruses. Intranasal (i.n.) treatment of t he H1N1 virus infection with 30 or 60 mg/kg of body weight/day, three times daily for 5 days, beginning 4 h pre- or 8 h post-virus exposure, was effective in preventing death, reducing the arterial oxygen decli ne, and inhibiting lung consolidation, Virus titers in the lungs deter mined on day 5 were reduced by up to 1.5 log(10) in treated groups, bu t considerable variation in the titers of the recovered virus was seen , The H3N2 virus infection was treated i.n. with 30, 60, or 120 mg of peptide 6/kg/day by using the above-mentioned delayed initiation treat ment schedule, and similar protection was seen, although lung virus ti ters were not reduced in the day-5 assay, Peptide 6 was well tolerated at doses up to 60 mg/kg/day, This zinc finger peptide may provide a n ew class of antivirals effective against influenza virus.