About: A major global effort is currently ongoing to search for therapeutics and vaccines to treat or prevent infection by the SARS-CoV-2 virus. Repurposing existing entities is one attractive approach. The heparan sulfate mimetic pixatimod is a clinical-stage synthetic sulfated compound that is a potent inhibitor of the glycosidase heparanase, and has known anti-cancer, anti-inflammatory and also antiviral properties. Here we show that pixatimod binds directly to the SARS-CoV-2 spike protein S1 receptor binding domain (RBD) and alters its conformation. Notably, this site overlaps with the known ACE2 binding site in the S1 RBD. We find that pixatimod inhibits binding of recombinant S1 RBD to Vero cells which express the ACE2 receptor. Moreover, in assays with three different isolates of live SARS-CoV-2 virus we show that pixatimod effectively inhibits viral infection of Vero cells. Importantly, its potency is well within its safe therapeutic dose range. These data provide evidence that pixatimod is a potent antiviral agent against SARS-CoV-2. Together with its other known activities this provides a strong rationale for its clinical investigation as a new multimodal therapeutic for the current COVID-19 pandemic.   Goto Sponge  NotDistinct  Permalink

An Entity of Type : fabio:Abstract, within Data Space : wasabi.inria.fr associated with source document(s)

AttributesValues
type
value
  • A major global effort is currently ongoing to search for therapeutics and vaccines to treat or prevent infection by the SARS-CoV-2 virus. Repurposing existing entities is one attractive approach. The heparan sulfate mimetic pixatimod is a clinical-stage synthetic sulfated compound that is a potent inhibitor of the glycosidase heparanase, and has known anti-cancer, anti-inflammatory and also antiviral properties. Here we show that pixatimod binds directly to the SARS-CoV-2 spike protein S1 receptor binding domain (RBD) and alters its conformation. Notably, this site overlaps with the known ACE2 binding site in the S1 RBD. We find that pixatimod inhibits binding of recombinant S1 RBD to Vero cells which express the ACE2 receptor. Moreover, in assays with three different isolates of live SARS-CoV-2 virus we show that pixatimod effectively inhibits viral infection of Vero cells. Importantly, its potency is well within its safe therapeutic dose range. These data provide evidence that pixatimod is a potent antiviral agent against SARS-CoV-2. Together with its other known activities this provides a strong rationale for its clinical investigation as a new multimodal therapeutic for the current COVID-19 pandemic.
subject
  • Virology
  • Glycobiology
  • Anti-inflammatory agents
part of
is abstract of
is hasSource of
Faceted Search & Find service v1.13.91 as of Mar 24 2020


Alternative Linked Data Documents: Sponger | ODE     Content Formats:       RDF       ODATA       Microdata      About   
This material is Open Knowledge   W3C Semantic Web Technology [RDF Data]
OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software