|Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2011: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2010: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2009: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
During the period(April, 2008.March 2012) of this grant, we clarified several new mechanisms on the hemagglutinin(HA) mutations responsible for the binding of highly pathogenic influenza virus(H5N1 subtype) to human type receptors and got progress on the drug discovery for influenza.
(1) We identified several type of amino acid substitutions in the HA(H5) spike of highly pathogenic avian influenza viruses(H5N1 subtype) isolated from not only "patients" but also from "birds" that increase their human-type receptor(Neu5Acα2, 6Gal) specificity Viruses in those sublineages exhibited increased attachment and infectivity in the human respiratory tract. We also identified an experimental reassortant H5 HA/H1N1 virus. comprising H5 HA(from an H5N1 virus) with only four amino acid mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus. that exhibited increased attachment to the human type receptor and was capable of "droplet transmission in a ferret model". Our findings may help to advance our understanding of the mechanisms and evolutionary pathways that contribute to avian influenza virus transmission in mammals.
(2) We also determined the fine chemical structures of H5N1 viral HA receptor N-linked sialo sugar chains of several target cells of H5N1 host animals, such as pig, dog, cat, embryonated chicken eggs.
(3) We developed more than 15 new synthetic and native compounds which inhibit human influenza virus receptor binding, replication and budding from the infected host cells.