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

Autor:	Leah Liu Wang, Leslie Estrada, Joshua Wiggins, Manu Anantpadma, J.J. Patten, Robert A. Davey, Shi-Hua Xiang
Rok vydání:	2022
Předmět:	Pharmacology Binding Sites Membrane Glycoproteins Intracellular Signaling Peptides and Proteins Endosomes Hemorrhagic Fever Ebola Virus Internalization Ebolavirus Filoviridae Ligands Cell Line Niemann-Pick C1 Protein Virology Humans Receptors Virus Carrier Proteins Viral Fusion Protein Inhibitors
Zdroj:	Antiviral research. 206
ISSN:	1872-9096
Popis:	Filoviruses enter cells through macropinocytosis 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::975d51d03c3c1a0f6433df2121401699 https://pubmed.ncbi.nlm.nih.gov/36007601 Zobrazit plný text záznamu Full Text from ScienceDirect