Structural insights into the design of novel anti-influenza therapies.

Structural insights into the design of novel anti-influenza therapies.
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DOI:
10.1038/s41594-018-0025-9
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发表时间:
2018-03
影响因子:
16.8
通讯作者:
Wilson IA
Wilson IA
中科院分区:
生物学1区
文献类型:
--
作者:
Wu NC;Wilson IA

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有限的治疗方法可用于应对未来流感大流行的出现,甚至有效地应对季节性流感的持续爆发。然而,最近的发现为设计新的疫苗和治疗方法带来了巨大的希望,包括更普遍的治疗方法的可能性。对这些进展的主要贡献来自结构生物学,特别是对流感血凝素(HA)的许多研究,HA是主要的表面抗原。HA的主要功能是使病毒能够进入宿主细胞,结构工作揭示了在进入过程中产生的各种HA构象形式。其他研究探索了人类广泛中和抗体(bnAb),设计的蛋白质,肽和小分子如何抑制和中和病毒。在这里,我们回顾了HA结构生物学的里程碑,以及最近来自广泛中和抗体的见解如何导致新疫苗和治疗方法的设计。
A limited arsenal of therapies is available to tackle the emergence of a future influenza pandemic or even to effectively deal with the continual outbreaks of seasonal influenza. However, recent findings hold great promise for design of novel vaccines and therapeutics, including the possibility of more universal treatments. A major contribution to those advances comes from structural biology, in particular from the many studies on influenza hemagglutinin (HA), the major surface antigen. The HA primary function is to enable the virus to enter host cells, and structural work has revealed the various HA conformational forms generated during the entry process. Other studies have explored how human broadly neutralizing antibodies (bnAbs), designed proteins, peptides and small molecules, can inhibit and neutralize the virus. Here we review milestones in HA structural biology and how the recent insights from broadly neutralizing antibodies are leading to design of novel vaccines and therapeutics.
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