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http://purl.uniprot.org/citations/35922434http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35922434http://www.w3.org/2000/01/rdf-schema#comment"The COVID-19 pandemic is exacting an increasing toll worldwide, with new SARS-CoV-2 variants emerging that exhibit higher infectivity rates and that may partially evade vaccine and antibody immunity. Rapid deployment of non-invasive therapeutic avenues capable of preventing infection by all SARS-CoV-2 variants could complement current vaccination efforts and help turn the tide on the COVID-19 pandemic. Here, we describe a novel therapeutic strategy targeting the SARS-CoV-2 RNA using locked nucleic acid antisense oligonucleotides (LNA ASOs). We identify an LNA ASO binding to the 5' leader sequence of SARS-CoV-2 that disrupts a highly conserved stem-loop structure with nanomolar efficacy in preventing viral replication in human cells. Daily intranasal administration of this LNA ASO in the COVID-19 mouse model potently suppresses viral replication (>80-fold) in the lungs of infected mice. We find that the LNA ASO is efficacious in countering all SARS-CoV-2 "variants of concern" tested both in vitro and in vivo. Hence, inhaled LNA ASOs targeting SARS-CoV-2 represents a promising therapeutic approach to reduce or prevent transmission and decrease severity of COVID-19 in infected individuals. LNA ASOs are chemically stable and can be flexibly modified to target different viral RNA sequences and could be stockpiled for future coronavirus pandemics."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.org/dc/terms/identifier"doi:10.1038/s41467-022-32216-0"xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Xu L."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Lee J.Y."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Kauppinen S."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Zhu C."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Harris E."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Chiu C."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Schaletzky J."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Rouskin S."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Gonzalez F."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Pinsky B.A."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Sadreyev R.I."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Fox D."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Ji F."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Stanley S."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Blish C.A."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Rustagi A."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Yamashiro L.H."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Wehri E."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Naar A.M."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Biering S.B."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Van Dis E."xsd:string
http://purl.uniprot.org/citations/35922434http://purl.uniprot.org/core/author"Nguyenla X."xsd:string