Design and Concise Synthesis of Halicyclamine-Inspired Bismacrocycles Targeting DedA Membrane Proteins

Abstract

DedA membrane proteins promote the formation of doublemembrane vesicles serving as replication platforms for RNA viruses, including SARS-CoV-2. Inspired by the only known inhibitor, halicyclamine A, we developed a concise biomimetic synthesis of halicyclamine-inspired macrocycles, identifying bis-macrocycles that suppress SARS-CoV-2 replication, while exhibiting DedAassociated activity in a bacterial overexpression assay.