{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":49,"searchCount":0},"additional":{"omics_type":["Unknown"],"submitter":["Rosenke K"],"pubmed_abstract":["<b>Background: </b>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.<br><br><b>Methods: </b>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.<br><br><b>Results: </b>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.<br><br><b>Conclusions: </b>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."],"journal":["The Journal of antimicrobial chemotherapy"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7717290"],"repository":["biostudies-literature"],"pubmed_title":["Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino oligomers."],"pmcid":["PMC7717290"],"pubmed_authors":["Rosenke K","Moulton HM","Hatlevig S","Stein DA","Feldmann H","Leventhal S","Hawman D"],"view_count":["49"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino oligomers.","description":"<b>Background: </b>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.<br><br><b>Methods: </b>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.<br><br><b>Results: </b>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.<br><br><b>Conclusions: </b>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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Nov","modification":"2021-02-20T09:58:29Z","creation":"2021-02-20T09:58:29Z"},"accession":"S-EPMC7717290","cross_references":{"pubmed":["33164048"],"doi":["10.1093/jac/dkaa460"]}}