β-Amyloid peptide (Aβ) self-associates into oligomers and fibrils, in a process that is believed to directly lead to neuronal death in Alzheimer’s disease. Compounds that bind to Aβ, and inhibit fibrillogenesis and neurotoxicity, are of interest as an anti-Alzheimer therapeutic strategy. Peptides are particularly attractive for this purpose, because they have advantages over small molecules in their ability to disrupt protein–protein interactions, yet they are amenable to tuning of their properties through chemical means, unlike antibodies. Self-complementation and peptide library screening are two strategies that have been employed in the search for peptides that bind to Aβ. We have taken a different approach, by designing Aβ-binding peptides using transthyretin (TTR) as a template. Previously, we demonstrated that a cyclic peptide, with sequence derived from the known Aβ-binding site on TTR, suppressed Aβ aggregation into fibrils and protected neurons against Aβ toxicity. Here, we searched for cyclic peptides with improved efficacy, by employing the algorithm TANGO, designed originally to identify amyloidogenic sequences in proteins. By using TANGO as a guide to predict the effect of sequence modifications on conformation and aggregation, we synthesized a significantly improved cyclic peptide. We demonstrate that the peptide, in binding to Aβ, redirects Aβ toward protease-sensitive, nonfibrillar aggregates. Cyclic peptides designed using this strategy have attractive solubility, specificity, and stability characteristics.

Coronavirus disease 2019 (COVID-19) can cause acute respiratory distress syndrome (ARDS) that is associated with high mortality among patients requiring invasive mechanical ventilation. We present a case of a 56-year-old male with hypertension and obesity who presented with chest pain from COVID-19. The patient required endotracheal intubation due to worsening hypoxia and remained intubated for 33 days. Tracheostomy placement was delayed in part due to persistent COVID-19 positive testing until hospital day 37. The patient required a total of 52 days in the ICU prior to discharge to a rehabilitation facility. This case highlights the extensive resources needed for critically ill patients with COVID-19 and the long duration that patients may test positive for the virus after onset of symptoms. It also raises questions about the timing and safety of tracheostomy placement among those patients requiring mechanical ventilation from COVID-19.

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