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10.1016/j.meegid.2020.104474

http://scihub22266oqcxt.onion/10.1016/j.meegid.2020.104474
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suck abstract from ncbi


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pmid32712315      Infect+Genet+Evol 2020 ; 85 (ä): 104474
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  • Decoding the proteome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for cell-penetrating peptides involved in pathogenesis or applicable as drug delivery vectors #MMPMID32712315
  • Hemmati S; Behzadipour Y; Haddad M
  • Infect Genet Evol 2020[Nov]; 85 (ä): 104474 PMID32712315show ga
  • Synthetic or natural derived cell-penetrating peptides (CPPs) are vastly investigated as tools for the intracellular delivery of membrane-impermeable molecules. As viruses are intracellular obligate parasites, viral originated CPPs have been considered as suitable intracellular shuttling vectors for cargo transportation. A total of 310 CPPs were identified in the proteome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Screening the proteome of the cause of COVID-19 reveals that SARS-CoV-2 CPPs (SCV2-CPPs) span the regions involved in replication, protein-nucleotide and protein-protein interaction, protein-metal ion interaction, and stabilization of homo/hetero-oligomers. However, to find the most appropriate peptides as drug delivery vectors, one might face several hurdles. Computational analyses showed that 94.3% of the identified SCV2-CPPs are non-toxins, and 38% are neither antigenic nor allergenic. Interestingly, 36.70% of SCV2-CPPs were resistant to all four groups of protease families. Nearly 1/3 of SCV2-CPPs had sufficient inherent or induced helix and sheet conformation leading to increased uptake efficiency. Heliquest lipid-binding discrimination factor revealed that 44.30% of the helical SCV2-CPPs are lipid-binding helices. Although Cys-rich derived CPPs of helicase (NSP13) can potentially fold into a cyclic conformation in endosomes with a higher rate of endosomal release, the most optimal SCV2-CPP candidates as vectors for drug delivery were SCV2-CPP118, SCV2-CPP119, SCV2-CPP122, and SCV2-CPP129 of NSP12 (RdRp). Ten experimentally validated viral-derived CPPs were also used as the positive control to check the scalability and reliability of our protocol in SCV2-CPP retrieval. Some peptides with a cell-penetration ability known as bioactive peptides are adopted as biotherapeutics themselves. Therefore, 59.60%, 29.63%, and 32.32% of SCV2-CPPs were identified as potential antibacterial, antiviral, and antifungals, respectively. While 63.64% of SCV2-CPPs had immuno-modulatory properties, 21.89% were recognized as anti-cancers. Conclusively, the workflow of this study provides a platform for profound screening of viral proteomes as a rich source of biotherapeutics or drug delivery carriers.
  • |Antiviral Agents/pharmacology/therapeutic use[MESH]
  • |Cell-Penetrating Peptides/chemistry/*metabolism[MESH]
  • |Computational Biology/*methods[MESH]
  • |Drug Evaluation, Preclinical[MESH]
  • |Humans[MESH]
  • |Protein Folding[MESH]
  • |Protein Structure, Secondary[MESH]
  • |Proteome/drug effects[MESH]
  • |SARS-CoV-2/drug effects/metabolism/*pathogenicity[MESH]
  • |Support Vector Machine[MESH]
  • |Viral Proteins/chemistry/metabolism[MESH]


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