Anti-Niemann Pick C1 Single-Stranded Oligonucleotides with Locked Nucleic Acids Potently Reduce Ebola Virus Infection In Vitro.

ABSTRACT: Ebola virus is the causative agent of Ebola virus disease, a severe, often fatal illness in humans. So far, there are no US Food and Drug Administration (FDA)-approved therapeutics directed against Ebola virus. Here, we selected the host factor Niemann-Pick C1 (NPC1), which has been shown to be essential for Ebola virus entry into host cytoplasm, as a therapeutic target for suppression by locked nucleic acid-modified antisense oligonucleotides. Screening of antisense oligonucleotides in human and murine cell lines led to identification of candidates with up to 94% knockdown efficiency and 50% inhibitory concentration (IC₅₀) values in the submicromolar range. Selected candidate oligonucleotides led to efficient NPC1 protein knockdown in vitro without alteration of cell viability.

SUBMITTER: Sadewasser A 

PROVIDER: S-EPMC6529764 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature