Discovery of Pentacyclic Triterpenoids as Potential Entry Inhibitors of Influenza Viruses
Citations Over TimeTop 10% of 2014 papers
Abstract
Entry inhibitors are of particular importance in current efforts to develop a new generation of anti-influenza virus drugs. Here we report certain pentacyclic triterpenes exhibiting conserved structure features and with in vitro anti-influenza virus activity comparable to and even higher than that of oseltamivir. Mechanistic studies indicated that these lead triterpenoids bind tightly to the viral envelope hemagglutinin (HA), disrupting the interaction of HA with the sialic acid receptor and thus the attachment of viruses to host cells. Docking studies suggest that the binding pocket within HA for sialic acid receptor potentially acts as a targeting domain, and this is supported by structure-activity data, sialic acid competition studies, and broad anti-influenza spectrum as well as less induction of drug resistance. Our study might establish the importance of triterpenoids for development of entry inhibitors of influenza viruses.
Related Papers
- → Entry of Bluetongue Virus Capsid Requires the Late Endosome-specific Lipid Lysobisphosphatidic Acid(2016)35 cited
- → Lipid Membranes Facilitate Conformational Changes Required for Reovirus Cell Entry(2015)32 cited
- → Viral Entry Inhibitors Targeting Six-Helical Bundle Core againstHighly Pathogenic Enveloped Viruses with Class I Fusion Proteins(2021)15 cited
- → Analysis of Cytomegalovirus Ligands, Receptors, and the Entry Pathway(2003)8 cited
- → ‘Entry’ of Enveloped Viruses into Liposomes(1988)4 cited