PubMed:33125711 JSONTXT 19 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-118 Sentence denotes Unfractionated heparin inhibits live wild-type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations.
T2 119-142 Sentence denotes BACKGROUND AND PURPOSE:
T3 143-237 Sentence denotes Currently there are no licensed vaccines and limited antivirals for the treatment of COVID-19.
T4 238-343 Sentence denotes Heparin (delivered systemically) is currently used to treat anticoagulant anomalies in COVID-19 patients.
T5 344-493 Sentence denotes In addition, in the UK, Brazil and Australia, nebulised unfractionated heparin (UFH) is being trialled in COVID-19 patients as a potential treatment.
T6 494-634 Sentence denotes A systematic comparison of the potential antiviral effect of various heparin preparations on live wild-type SARS-CoV-2, in vitro, is needed.
T7 635-657 Sentence denotes EXPERIMENTAL APPROACH:
T8 658-913 Sentence denotes Seven different heparin preparations including UFH and low molecular weight heparins (LMWH) of porcine or bovine origin were screened for antiviral activity against live SARS-CoV-2 (Australia/VIC01/2020) using a plaque inhibition assay with Vero E6 cells.
T9 914-1101 Sentence denotes Interaction of heparin with spike protein RBD was studied using differential scanning fluorimetry, and the inhibition of RBD binding to human ACE2 protein using ELISA assays was examined.
T10 1102-1114 Sentence denotes KEY RESULTS:
T11 1115-1297 Sentence denotes All the UFH preparations had potent antiviral effects, with IC50 values ranging between 25-41 μg ml-1 whereas LMWHs were less inhibitory by ~150-fold (IC50 range 3.4 - 7.8 mg ml-1 ).
T12 1298-1483 Sentence denotes Mechanistically we observed that heparin binds and destabilizes the RBD protein, and furthermore we show heparin directly inhibits the binding of RBD to the human ACE2 protein receptor.
T13 1484-1513 Sentence denotes CONCLUSIONS AND IMPLICATIONS:
T14 1514-1647 Sentence denotes This comparison of clinically relevant heparins shows UFH has significantly stronger SARS-CoV-2 antiviral activity compared to LMWHs.
T15 1648-1737 Sentence denotes UFH acts to directly inhibit binding of spike protein to the human ACE2 protein receptor.
T16 1738-1862 Sentence denotes Overall the data strongly support further clinical investigation of UFH as a potential treatment for patients with COVID-19.