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|Title||Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino oligomers.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Rosenke, K, Leventhal, S, Moulton, HM, Hatlevig, S, Hawman, D, Feldmann, H, Stein, DA|
|Journal||J Antimicrob Chemother|
|Date Published||2021 01 19|
|Keywords||Animals, Antiviral Agents, Cell Survival, Cell-Penetrating Peptides, Chlorocebus aethiops, COVID-19, Cytopathogenic Effect, Viral, Morpholinos, SARS-CoV-2, Vero Cells, Virus Replication|
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 TCID50 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 log10 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.
|Alternate Journal||J Antimicrob Chemother|
|PubMed Central ID||PMC7717290|