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Long-chain polyphosphates impair SARS-CoV-2 infection and replication
DC Field | Value | Language |
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dc.contributor.author | 정재호 | - |
dc.date.accessioned | 2021-12-28T17:52:21Z | - |
dc.date.available | 2021-12-28T17:52:21Z | - |
dc.date.issued | 2021-07 | - |
dc.identifier.issn | 1937-9145 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/187309 | - |
dc.description.abstract | Inorganic polyphosphates (polyPs) are linear polymers composed of repeated phosphate (PO4 3-) units linked together by multiple high-energy phosphoanhydride bonds. In addition to being a source of energy, polyPs have cytoprotective and antiviral activities. Here, we investigated the antiviral activities of long-chain polyPs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In molecular docking analyses, polyPs interacted with several conserved amino acid residues in angiotensin-converting enzyme 2 (ACE2), the host receptor that facilitates virus entry, and in viral RNA-dependent RNA polymerase (RdRp). ELISA and limited proteolysis assays using nano- LC-MS/MS mapped polyP120 binding to ACE2, and site-directed mutagenesis confirmed interactions between ACE2 and SARS-CoV-2 RdRp and identified the specific amino acid residues involved. PolyP120 enhanced the proteasomal degradation of both ACE2 and RdRp, thus impairing replication of the British B.1.1.7 SARS-CoV-2 variant. We thus tested polyPs for functional interactions with the virus in SARS-CoV-2-infected Vero E6 and Caco2 cells and in primary human nasal epithelial cells. Delivery of a nebulized form of polyP120 reduced the amounts of viral positive-sense genomic and subgenomic RNAs, of RNA transcripts encoding proinflammatory cytokines, and of viral structural proteins, thereby presenting SARS-CoV-2 infection in cells in vitro. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | American Association for the Advancement of Science | - |
dc.relation.isPartOf | SCIENCE SIGNALING | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Administration, Inhalation | - |
dc.subject.MESH | Amino Acid Sequence | - |
dc.subject.MESH | Angiotensin-Converting Enzyme 2 / chemistry | - |
dc.subject.MESH | Angiotensin-Converting Enzyme 2 / metabolism | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antiviral Agents / administration & dosage | - |
dc.subject.MESH | Antiviral Agents / chemistry | - |
dc.subject.MESH | Antiviral Agents / pharmacology* | - |
dc.subject.MESH | COVID-19 / drug therapy* | - |
dc.subject.MESH | COVID-19 / metabolism | - |
dc.subject.MESH | COVID-19 / virology | - |
dc.subject.MESH | Caco-2 Cells | - |
dc.subject.MESH | Chlorocebus aethiops | - |
dc.subject.MESH | Coronavirus RNA-Dependent RNA Polymerase / chemistry | - |
dc.subject.MESH | Coronavirus RNA-Dependent RNA Polymerase / genetics | - |
dc.subject.MESH | Coronavirus RNA-Dependent RNA Polymerase / metabolism | - |
dc.subject.MESH | Cytokines / metabolism | - |
dc.subject.MESH | HEK293 Cells | - |
dc.subject.MESH | Host Microbial Interactions / drug effects | - |
dc.subject.MESH | Host Microbial Interactions / genetics | - |
dc.subject.MESH | Host Microbial Interactions / physiology | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | In Vitro Techniques | - |
dc.subject.MESH | Models, Biological | - |
dc.subject.MESH | Molecular Docking Simulation | - |
dc.subject.MESH | Nebulizers and Vaporizers | - |
dc.subject.MESH | Polyphosphates / administration & dosage | - |
dc.subject.MESH | Polyphosphates / chemistry | - |
dc.subject.MESH | Polyphosphates / pharmacology* | - |
dc.subject.MESH | Proteasome Endopeptidase Complex / metabolism | - |
dc.subject.MESH | Protein Interaction Domains and Motifs | - |
dc.subject.MESH | Proteolysis / drug effects | - |
dc.subject.MESH | RNA, Viral / genetics | - |
dc.subject.MESH | RNA, Viral / metabolism | - |
dc.subject.MESH | SARS-CoV-2 / drug effects* | - |
dc.subject.MESH | SARS-CoV-2 / genetics | - |
dc.subject.MESH | SARS-CoV-2 / physiology | - |
dc.subject.MESH | Sequence Homology, Amino Acid | - |
dc.subject.MESH | Signal Transduction / drug effects | - |
dc.subject.MESH | Vero Cells | - |
dc.subject.MESH | Virus Replication / drug effects | - |
dc.title | Long-chain polyphosphates impair SARS-CoV-2 infection and replication | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Surgery (외과학교실) | - |
dc.contributor.googleauthor | Veronica Ferrucci | - |
dc.contributor.googleauthor | Dae-Young Kong | - |
dc.contributor.googleauthor | Fatemeh Asadzadeh | - |
dc.contributor.googleauthor | Laura Marrone | - |
dc.contributor.googleauthor | Angelo Boccia | - |
dc.contributor.googleauthor | Roberto Siciliano | - |
dc.contributor.googleauthor | Giuseppina Criscuolo | - |
dc.contributor.googleauthor | Camilla Anastasio | - |
dc.contributor.googleauthor | Fabrizio Quarantelli | - |
dc.contributor.googleauthor | Marika Comegna | - |
dc.contributor.googleauthor | Ida Pisano | - |
dc.contributor.googleauthor | Margherita Passariello | - |
dc.contributor.googleauthor | Ilaria Iacobucci | - |
dc.contributor.googleauthor | Rosa Della Monica | - |
dc.contributor.googleauthor | Barbara Izzo | - |
dc.contributor.googleauthor | Pellegrino Cerino | - |
dc.contributor.googleauthor | Giovanna Fusco | - |
dc.contributor.googleauthor | Maurizio Viscardi | - |
dc.contributor.googleauthor | Sergio Brandi | - |
dc.contributor.googleauthor | Bianca Maria Pierri | - |
dc.contributor.googleauthor | Giorgia Borriello | - |
dc.contributor.googleauthor | Claudia Tiberio | - |
dc.contributor.googleauthor | Luigi Atripaldi | - |
dc.contributor.googleauthor | Martina Bianchi | - |
dc.contributor.googleauthor | Giovanni Paolella | - |
dc.contributor.googleauthor | Ettore Capoluongo | - |
dc.contributor.googleauthor | Giuseppe Castaldo | - |
dc.contributor.googleauthor | Lorenzo Chiariotti | - |
dc.contributor.googleauthor | Maria Monti | - |
dc.contributor.googleauthor | Claudia De Lorenzo | - |
dc.contributor.googleauthor | Kyong-Seop Yun | - |
dc.contributor.googleauthor | Stefano Pascarella | - |
dc.contributor.googleauthor | Jae-Ho Cheong | - |
dc.contributor.googleauthor | Hong-Yeoul Kim | - |
dc.contributor.googleauthor | Massimo Zollo | - |
dc.identifier.doi | 10.1126/scisignal.abe5040 | - |
dc.contributor.localId | A03717 | - |
dc.relation.journalcode | J02644 | - |
dc.identifier.eissn | 1945-0877 | - |
dc.identifier.pmid | 34230209 | - |
dc.contributor.alternativeName | Cheong, Jae Ho | - |
dc.contributor.affiliatedAuthor | 정재호 | - |
dc.citation.volume | 14 | - |
dc.citation.number | 690 | - |
dc.citation.startPage | eabe5040 | - |
dc.identifier.bibliographicCitation | SCIENCE SIGNALING, Vol.14(690) : eabe5040, 2021-07 | - |
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