Design and Synthesis of Oleanolic Acid Trimers to Enhance Inhibition of Influenza Virus Entry.

ABSTRACT: Influenza is a major threat to millions of people worldwide. Entry inhibitors are of particular interest for the development of novel therapeutic strategies for influenza. We have previously discovered oleanolic acid (OA) to be a mild influenza hemagglutinin (HA) inhibitor. In this work, inspired by the 3D structure of HA as a homotrimeric receptor, we designed and synthesized 15 OA trimers with different linkers and central region via the copper-catalyzed azide-alkyne cycloaddition reaction. All of the OA trimers were evaluated for their antiviral activities in vitro, and 12c, 12e, 13c, and 13d were observed to exhibit robust potency (IC₅₀ in the submicromolar range) against influenza A/WSN/33 (H1N1) virus that was stronger than that observed with os

SUBMITTER: Shao L 

PROVIDER: S-EPMC8591716 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature