INFLUENZA VIRUS-INHIBITORY EFFECTS OF A SERIES OF GERMANIUM-CENTERED AND SILICON-CENTERED POLYOXOMETALATES

A series of germanium- or silicon-centred heteropolytungstates (polyox ometalates) with the Barrel, Keggin or double Keggin structure were ev aluated in vitro for their effects against influenza A (IV-A) and B (I V-B) viruses. Their 50% effective concentrations (EC(50)) against rece nt isolates of IV-A (H1N1) and IV-B ranged from 0.1 to 7.8 mu M; again st IV-A (H3N2), the EC(50) concentrations were often 10-fold higher. R ecent clinical isolates of IV-A were generally more susceptible to the se antiviral effects than older, laboratory-adapted strains. These exp eriments used inhibition of viral CPE in MDCK cells as determined micr oscopically and by Neutral Red (NR) uptake. Virus yield reduction stud ies indicated the 90% effective concentrations (EC(90)) ranged from 0. 2 to 32 mu M against these viruses. Cytotoxic or cell inhibitory conce ntrations (CC50), determined by NR uptake and total cell count, ranged from 38 to 189 mu M, indicating high selective indices for some of th ese compounds. Altering time of addition of an active compound relativ e to infecting cells with IV-A (H1N1) showed greatest efficacy when gi ven early in viral replication. Five of the most active polyoxometalat es were evaluated against IV-B infections in mice using intraperitonea l treatment beginning 4 h prior to virus exposure. Two of the compound s, one with the Barrel structure and the other with a double Keggin st ructure, were particularly inhibitory, preventing deaths, reducing art erial oxygen decline and lowering lung consolidation. Lung virus titre s were reduced by a maximum of 0.7 log(10). Therapy initiated 8 h post -virus exposure was not effective against this in vivo infection.