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. |