Unfractionated heparin inhibits live wild-type SARS-CoV-2 cell
infectivity at therapeutically relevant concentrations.
Abstract
Background and Purpose: Currently there are no licensed vaccines and
limited antivirals for the treatment of COVID-19. Heparin (delivered
systemically) is currently being used to treat anticoagulant anomalies
in COVID-19 patients. In addition, in the UK, nebulised unfractionated
heparin (UFH) is currently being trialled in COVID-19 patients as a
potential treatment. A systematic comparison of the potential antiviral
effect of various heparin preparations on live wild-type SARS-CoV-2, in
vitro, is thus urgently needed. Experimental Approach: A range of
heparin preparations both UFH (n=4) and low molecular weight heparins
(LMWH) (n=3) of porcine or bovine origin were screened for antiviral
activity against live SARS-CoV-2 (Victoria/01/2020) using a plaque
reduction neutralisation assay and Vero E6 cells. ND50 values for each
heparin were calculated using a mid-point probit analysis. Key Results:
UFH had potent antiviral effects, with ND50 values of 12.5 and 23 μg/ml
for two porcine mucosal UFH tested. Bovine mucosal UFH had similar
antiviral effects although it was ~50% less active
(ND50, 50-75 μg/ml). In contrast, LMWHs such as Clexane and Fragmin were
markedly less active by ~100-fold (ND50 values of
2.6-6.8 mg/ml). Conclusions and Implications: This comparison of a panel
of clinically relevant heparins, including the UFH preparation under
trial in the UK, demonstrated that distinct products exhibit different
degrees of antiviral activity against live SARS-CoV-2. Porcine mucosal
UFH has the strongest antiviral activity followed by bovine mucosal UFH,
whereas LMWHs had the lowest amount of antiviral activity (by 100-fold).
Overall the data strongly support further clinical investigation of UFH
as a potential treatment for patients with COVID-19.