PropertyValue
?:abstract
  • BACKGROUND: As the causative agent of COVID-19, SARS-CoV-2 is a pathogen of immense importance to global public health. Development of innovative direct-acting antiviral agents is sorely needed to address this virus. Peptide-conjugated morpholino oligomers (PPMO) are antisense compounds composed of a phosphorodiamidate morpholino oligomer covalently conjugated to a cell-penetrating peptide. PPMO require no delivery assistance to enter cells and are able to reduce expression of targeted RNA through sequence-specific steric blocking. METHODS: Five PPMO designed against sequences of genomic RNA in the SARS-CoV-2 5′-untranslated region and a negative control PPMO of random sequence were synthesized. Each PPMO was evaluated for its effect on the viability of uninfected cells and its inhibitory effect on the replication of SARS-CoV-2 in Vero-E6 cell cultures. Cell viability was evaluated with an ATP-based method using a 48 h PPMO treatment time. Viral growth was measured with quantitative RT–PCR and TCID(50) infectivity assays from experiments where cells received a 5 h PPMO treatment time. RESULTS: PPMO designed to base-pair with sequence in the 5′ terminal region or the leader transcription regulatory sequence region of SARS-CoV-2 genomic RNA were highly efficacious, reducing viral titres by up to 4–6 log(10) in cell cultures at 48–72 h post-infection, in a non-toxic and dose-responsive manner. CONCLUSIONS: The data indicate that PPMO have the ability to potently and specifically suppress SARS-CoV-2 growth and are promising candidates for further preclinical development.
is ?:annotates of
?:creator
?:doi
  • 10.1093/jac/dkaa460
?:doi
?:journal
  • J_Antimicrob_Chemother
?:license
  • no-cc
?:pdf_json_files
  • document_parses/pdf_json/6234f754f21d209f04c99e67b24a859c8e6629ec.json
?:pmc_json_files
  • document_parses/pmc_json/PMC7717290.xml.json
?:pmcid
?:pmid
?:pmid
  • 33164048.0
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:sha_id
?:source
  • Medline; PMC
?:title
  • Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino oligomers
?:type
?:year
  • 2020-11-09

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