Antiviral peptides targeting the west nile virus envelope protein

Antiviral peptides targeting the west nile virus envelope protein
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DOI:
10.1128/jvi.01840-06
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发表时间:
2007-02-01
影响因子:
5.4
通讯作者:
Fikrig, Erol
Fikrig, Erol
中科院分区:
医学2区
文献类型:
--
作者:
Bai, Fengwei;Town, Terrence;Fikrig, Erol

文献摘要

被引文献

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西尼罗河病毒(WNV)可引起致命的小鼠和人类脑炎。病毒包膜蛋白与宿主细胞相互作用。因此,小鼠脑cDNA噬菌体展示文库与WNV包膜蛋白探测,导致在几个粘附肽的鉴定。其中,肽1在体外以67 μ M的50%抑制浓度防止WNV感染,并且还抑制相关黄病毒、登革病毒的感染。肽9是肽1的衍生物,在体外是WNV的特别有效的抑制剂,50%抑制浓度为2.6 μ M。此外,与对照动物相比,用已与肽9孵育的WNV攻击的小鼠具有降低的病毒血症和死亡率。肽9穿透小鼠血脑屏障并在脑实质中被发现,这意味着它可能在中枢神经系统中具有抗病毒活性。这些短肽作为开发西尼罗河脑炎和潜在的其他黄病毒的新疗法的基础。
West Nile virus (WNV) can cause fatal murine and human encephalitis. The viral envelope protein interacts with host cells. A murine brain cDNA phage display library was therefore probed with WNV envelope protein, resulting in the identification of several adherent peptides. Of these, peptide 1 prevented WNV infection in vitro with a 50% inhibition concentration of 67 mu M and also inhibited infection of a related flavivirus, dengue virus. Peptide 9, a derivative of peptide 1, was a particularly potent inhibitor of WNV in vitro, with a 50% inhibition concentration of 2.6 mu M. Moreover, mice challenged with WNV that had been incubated with peptide 9 had reduced viremia and fatality compared with control animals. Peptide 9 penetrated the murine blood-brain barrier and was found in the brain parenchyma, implying that it may have antiviral activity in the central nervous system. These short peptides serve as the basis for developing new therapeutics for West Nile encephalitis and, potentially, other flaviviruses.