摘要
目前抗流感病毒的药物和疫苗受到病毒耐药性、疫苗滞后性等诸多因素的限制,使能阻止病毒进入细胞的流感病毒进入抑制剂成为当前研究的热点。唾液酸是HA的受体,但研究表明唾液酸并不适合作为研制流感病毒进入抑制剂的结构模型。研究发现流感病毒的HA受体结合位点抗体能与HA受体结合位点的保守氨基酸残基结合,能有效的抑制流感病毒感染宿主。针对HA受体结合位点的突变逃逸株失去感染能力。因此,可用HA受体结合位点抗体作为流感病毒进入抑制剂的模型,研制流感病毒抑制剂。
At present,the anti flu drugs and vaccines were restricted by drug resistance,hysteresis and other factors,so the influenza virus entry inhibitors which can prevent virus entry host cell become a research hotspot.Sialic acid is the receptor of HA,but it not suitable as a structure model of influenza virus entry inhibitors.The study found that the HA receptor binding sites' s antibody can binding the conserved amino acid residues,can effectively inhibit influenza virus infection.The HA receptor binding site mutation escape mutant loses the ability of infection.So the HA receptor binding sites' s antibody is a suitable model for inhibitors of influenza virus entry
引文
[1]W.WEIS,J.H.BROWN,S.CUSACK,et al.Structure of the influenza virus haemagglutinin complexed with its receptor,sialic acid[J].Nature,1988,333(6172):426-431.
[2]XU RUI,A.Wilson.Structural characterization of an early fusion intermediate of influenza virus hemagglutinin[J].J Virol,2011,85(10):5172-5182.
[3]MIKHAIL Matrosovich,KLENK Hans-Dieter.Natural and synthetic sialic acid-containing inhibitors of influenza virus receptor binding[J].Rev Med Virol,2003,13(2):85-97.
[4]NOBUKO Ohshima,YOSHITAKE Iba,RITSUKO Kubota Koketsu,et al.Naturally occurring antibodies in humans can neutralize a variety of influenza virus strains,including H3,H1,H2,and H5[J].J Virol,2011,85(21):11047-11057.
[5]KRAUSEA Jens C,TSHIDI Tsibanec,TERRENCE M,et al.Human monoclonal antibodies to pandemic 1957H2N2 and pandemic 1968 H3N2 influenza viruses[J].J Virol,2012,86(11):6334-6340.
[6]WHITTLE James R,ZHANG Ruijun,SURENDER Khuranac,et al.Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin[J].PNAS,2011,108(34):14216-14221.
[7]EKIERT Damian C,KASHYAP Arun K.,JOHN Steel,et al.Cross-neutralization of influenza A viruses mediated by a single antibody loop[J].Nature,2012,489(7417):526-532.
[8]LEEA Peter S.,REIKO Yoshidab,EKIERTA Damian C.,et al.Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity[J].Proc Natl Acad Sci USA,2012,109(42):17040-17045.
[9]XU Rui,KRAUSE Jens C,RYAN Mc Bride,et al.A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin[J].Nat Struct Mol Biol,2013,20(3):363-370.