Inhibitors of Viral Membrane Fusion

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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.