Biochem Pharmacol . The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations

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Biochem Pharmacol


. 2020 Sep 6;114215.
doi: 10.1016/j.bcp.2020.114215. Online ahead of print.
The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations


Meik Neufurth ¹ , Xiaohong Wang ² , Emad Tolba ¹ , Ingo Lieberwirth ³ , Shunfeng Wang ¹ , Heinz C Schr?der ¹ , Werner E G M?ller ⁴



Affiliations

• PMID: 32905794
• DOI: 10.1016/j.bcp.2020.114215

Abstract

Inorganic polyphosphate (polyP) is a morphogenetically active and metabolic energy-delivering physiological polymer that is released from blood platelets. Here, we show that polyP efficiently inhibits the binding of the envelope spike (S)-protein of the coronavirus SARS-CoV-2, the causative agent of COVID-19, to its host cell receptor ACE2 (angiotensin-converting enzyme 2). To stabilize polyP against the polyP-degrading alkaline phosphatase, the soluble polymer was encapsulated in silica/polyP nanoparticles. Applying a binding assay, soluble Na-polyP (sizes of 40 P_i and of 3 P_i units) as well as silica-nanoparticle-associated polyP significantly inhibit the interaction of the S-protein with ACE2 at a concentration of 1 ?g/mL, close to the level present in blood. This inhibition is attributed to an interaction of polyP with a basic amino acid stretch on the surface of the receptor binding domain of S-protein. PolyP retains its activity in a flushing solution, opening a new strategy for the prevention and treatment of SARS-CoV-2 infection in the oropharyngeal cavity. The data suggest that supplementation of polyP might contribute to a strengthening of the human innate immunity system in compromised, thrombocytopenic COVID-19 patients.

Keywords: Binding assay; COVID-19; Nanoparticles; Polyphosphate; SARS-CoV-2 spike S-protein.