Inhibitors of Viral Membrane Fusion

病毒膜融合抑制剂

• 批准号: 9556713
• 负责人: Federico Bernal
• 金额: $ 30.74万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9556713
• 关键词: Alpha Cell; Animals; Binding; Cell surface; Cells; Cessation of life; Collaborations; Cytoplasm; Doctor of Philosophy; Drug Kinetics; Ebola virus; Ebola-like Viruses; Elements; Endocytosis; Endosomes; Evaluation; Family; Filoviridae; Filovirus; GP2 gene; Genomics; Glycoproteins; Goals; Human; Impairment; In Vitro; Infection; Infection prevention; Liquid substance; Measures; Membrane; Membrane Fusion; Molecular; Molecular Conformation; National Institute of Allergy and Infectious Disease; Organ failure; Pathway interactions; Peptides; Permeability; Property; Spectrum Analysis; System; Testing; Validation; Viral; Viral Hemorrhagic Fevers; Virus; Virus Inhibitors; Work; base; design; prevent; research facility; septic

We designed a small family of three SEboV compounds by keeping contact residues intact and inserting the stapling elements away from any of the interfaces. CD spectroscopy demonstrated the alpha helical character of the peptides which was enhanced at lower pHs such as those measured inside a mature endosome. In collaboration with the group of Peter Jahrling, PhD at the Integrated Research Facility (part of the National Institute of Allergy and Infectious Disease), we tested the peptides for their ability to prevent infection. Results from the first round of tests suggested that two of the compounds successfully inhibited infection. Further, the compound that was not effective was later optimized to make it even more potent than the first two. Current work involves validation of the mechanism of action of the compounds and the evaluation of their pharmacokinetic properties.

我们通过保持接触残基完整并将钉合元件插入远离任何界面的方式，设计了一个由三种 SEboV 化合物组成的小系列。 CD 光谱证明了肽的 α 螺旋特征，该特征在较低 pH 值（例如在成熟内体中测量的 pH 值）下增强。我们与综合研究机构（国家过敏和传染病研究所的一部分）的 Peter Jahrling 博士团队合作，测试了这些肽预防感染的能力。第一轮测试的结果表明，其中两种化合物成功抑制了感染。此外，无效的化合物后来经过优化，使其比前两种更有效。目前的工作包括验证化合物的作用机制并评估其药代动力学特性。