Inhibitors of Viral Membrane Fusion

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来设计三种SEboV化合物的小家族。CD光谱证明了肽的α螺旋特征，其在较低pH下增强，例如在成熟内体内测量的那些。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，我们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地抑制了感染。此外，无效的化合物后来被优化，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和评价其药代动力学特性。

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.