Ligand-based design of peptide entry inhibitors targeting the endosomal receptor binding site of filoviruses

Antiviral Res. 2022 Aug 22:105399. doi: 10.1016/j.antiviral.2022.105399. Online ahead of print.ABSTRACTFiloviruses enter cells through micropinocytosis and trafficking into the endosomes in which they bind to the receptor Niemann-Pick C1 protein (NPC1) for membrane fusion and entry into the cytoplasm. The endosomal receptor-binding is critical step for filovirus entry. Designing inhibitors to block receptor binding will prevent viral entry. Using available binding structural information from the co-crystal structures of the viral GP with the receptor NPC1 or with monoclonal antibodies, we have conducted structure-based design of peptide inhibitors to target the receptor binding site (RBS). The designed peptides were tested for their inhibition activity against pseudo-typed or replication-competent viruses in a cell-based assay. The results indicate that these peptides exhibited strong activities against both Ebola and Marburg virus infection. It is expected that these peptides can be further developed for therapeutic use to treat filovirus infection and combat the outbreaks.PMID:36007601 | DOI:10.1016/j.antiviral.2022.105399

Source: Antiviral Research - August 25, 2022 Category: Virology Authors: Leah Liu Wang Leslie Estrada Joshua Wiggins Manu Anantpadma J J Patten Robert A Davey Shi-Hua Xiang Source Type: research