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INFLUENZA A AND B VIRUS REPLICATION-INHIBITING PEPTIDES

机译:甲型和乙型流感病毒复制抑制肽

摘要

A synthesized or isolated influenza virus replication-inhibiting peptide that competitively inhibits protein-protein interaction of the PA and PB1 of both influenza Virus Types A and B and novel in vitro binding screen to identify peptides with antiviral activity against influenza viruses of both type A and B is disclosed. In addition to the well-known pandemic influenza A viruses (such as the 1918 “Spanish” flu or H5N1), both type A and B viruses contribute greatly to the annual recurring epidemics that cause the vast majority of human cases and medical cost. Surprisingly, it was found that the novel virus replication-inhibiting, are able to inhibit protein-protein interaction of the PA and PB1 subunits of the heterotrimeric viral RNA polymerase complex of both influenza virus types A and B. The viral polymerase sub-unit interaction domain turned out as an effective target for the new antivirals, as correct assembly of the three viral polymerase subunits PB1, PB2 and PA is required for viral RNA synthesis and infectivity.
机译:一种合成的或分离的流感病毒复制抑制肽,可竞争性抑制A型和B型流感病毒的PA和PB1的蛋白质相互作用,并通过新颖的体外结合筛选来鉴定具有针对A型和B型流感病毒的抗病毒活性的肽公开了B。除了众所周知的大流行性甲型流感病毒(例如1918年的“西班牙”流感或H5N1)外,甲型和乙型病毒都对每年复发的流行病做出了巨大贡献,这些流行病导致了绝大多数的人类病例和医疗费用。令人惊讶地发现,抑制病毒复制的新型能够抑制甲型和乙型流感病毒的异源三聚体病毒RNA聚合酶复合物的PA和PB1亚基的蛋白质-蛋白质相互作用。病毒聚合酶亚基相互作用该域被证明是新抗病毒药物的有效靶点,因为病毒RNA合成和感染性需要三个病毒聚合酶亚基PB1,PB2和PA正确组装。

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