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

Autor: Wang LL; School of Veterinary Medicine and Biomedical Sciences, USA; Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA., Estrada L; School of Veterinary Medicine and Biomedical Sciences, USA; Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA., Wiggins J; Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA; School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA., Anantpadma M; Department of Microbiology & National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston, MA, 02115, USA., Patten JJ; Department of Microbiology & National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston, MA, 02115, USA., Davey RA; Department of Microbiology & National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston, MA, 02115, USA., Xiang SH; School of Veterinary Medicine and Biomedical Sciences, USA; Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA. Electronic address: sxiang2@unl.edu.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2022 Oct; Vol. 206, pp. 105399. Date of Electronic Publication: 2022 Aug 22.
DOI: 10.1016/j.antiviral.2022.105399
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE