Polysulfates Block SARS-CoV-2 Uptake through Electrostatic Interactions*.
Angew Chem Int Ed Engl
; 60(29): 15870-15878, 2021 07 12.
Article
in English
| MEDLINE | ID: covidwho-1265369
ABSTRACT
Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with an IC50 of 67â
µg mL-1 (approx. 1.6â
µm). This synthetic polysulfate exhibits more than 60-fold higher virus inhibitory activity than heparin (IC50 4084â
µg mL-1 ), along with much lower anticoagulant activity. Furthermore, in molecular dynamics simulations, we verified that LPGS can bind more strongly to the spike protein than heparin, and that LPGS can interact even more with the spike protein of the new N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into host cells can be blocked via electrostatic interactions, therefore LPGS can serve as a blueprint for the design of novel viral inhibitors of SARS-CoV-2.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Pentosan Sulfuric Polyester
/
Heparin
/
Virus Internalization
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Angew Chem Int Ed Engl
Year:
2021
Document Type:
Article
Affiliation country:
Anie.202102717
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