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10.1016/j.cell.2021.11.004

http://scihub22266oqcxt.onion/10.1016/j.cell.2021.11.004
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34838159!8577993!34838159
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suck abstract from ncbi


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pmid34838159      Cell 2021 ; 184 (25): 6022-6036.e18
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  • Identification of a therapeutic interfering particle-A single-dose SARS-CoV-2 antiviral intervention with a high barrier to resistance #MMPMID34838159
  • Chaturvedi S; Vasen G; Pablo M; Chen X; Beutler N; Kumar A; Tanner E; Illouz S; Rahgoshay D; Burnett J; Holguin L; Chen PY; Ndjamen B; Ott M; Rodick R; Rogers T; Smith DM; Weinberger LS
  • Cell 2021[Dec]; 184 (25): 6022-6036.e18 PMID34838159show ga
  • Viral-deletion mutants that conditionally replicate and inhibit the wild-type virus (i.e., defective interfering particles, DIPs) have long been proposed as single-administration interventions with high genetic barriers to resistance. However, theories predict that robust, therapeutic DIPs (i.e., therapeutic interfering particles, TIPs) must conditionally spread between cells with R(0) >1. Here, we report engineering of TIPs that conditionally replicate with SARS-CoV-2, exhibit R(0) >1, and inhibit viral replication 10- to 100-fold. Inhibition occurs via competition for viral replication machinery, and a single administration of TIP RNA inhibits SARS-CoV-2 sustainably in continuous cultures. Strikingly, TIPs maintain efficacy against neutralization-resistant variants (e.g., B.1.351). In hamsters, both prophylactic and therapeutic intranasal administration of lipid-nanoparticle TIPs durably suppressed SARS-CoV-2 by 100-fold in the lungs, reduced pro-inflammatory cytokine expression, and prevented severe pulmonary edema. These data provide proof of concept for a class of single-administration antivirals that may circumvent current requirements to continually update medical countermeasures against new variants.
  • |*COVID-19 Drug Treatment[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/pharmacology[MESH]
  • |COVID-19/metabolism[MESH]
  • |Cell Line[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Culture Media, Conditioned/pharmacology[MESH]
  • |Defective Interfering Viruses/*metabolism/pathogenicity[MESH]
  • |Drug Delivery Systems/methods[MESH]
  • |Epithelial Cells[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Mesocricetus[MESH]
  • |Nanoparticles/therapeutic use[MESH]
  • |SARS-CoV-2/drug effects/metabolism/pathogenicity[MESH]
  • |Vero Cells[MESH]


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