Til bevillingsoversigt

Identification of the Heparan Sulfate Binding Site in SARS-CoV-2

Carlsbergfondets internationaliseringsstipendier

What

The novel coronavirus SARS-CoV-2 binds and infects human cells with the help of a carbohydrate called heparan sulfate. This interaction is known to be mediated by the SARS-CoV-2 spike protein, however, the precise molecular interactions remain unclear. The aim of this project is to investigate the heparan sulfate-binding site of the spike protein and to identify the structure of the heparan sulfate ligand. This work may further elucidate the potential role of heparan sulfate in the SARS-CoV-2 tissue tropism.

Why

"The coronavirus disease 2019 (COVID-19) pandemic has caused morbidity, death, and widespread disruption to all aspects of society. There are currently no treatments or vaccines approved for any coronavirus. It is of dire need to understand the molecular mechanisms of the host-pathogen interactions to develop potential therapeutic compounds for the treatment and/or prevention of viral infections."

How

The project will be carried out at Jeffrey Esko's lab at the University of California, San Diego, CA, USA. The initial discovery of the SARS-CoV-2 and heparan sulfate interaction was made here, making this the ideal place to conduct this work. The studies will include spike protein mutational analysis, structural analysis of tissue heparan sulfate, immunohistochemistry, along with several types of ligand-binding assays. Furthermore, I will apply my expertise in carbohydrate structural analysis and identification of high affinity binding ligands to define the specific binding partner of SARS-CoV-2.

SSR

The COVID-19 pandemic has placed a significant burden on healthcare systems worldwide. Characterizing the host-pathogen interaction will provide tools and targets for exploring the mechanism of action of potential neutralizing molecular antibodies and small molecule antagonists of infection. Furthermore, these studies can be applied to investigate related coronaviruses and their mechanisms of viral entry for the prevention of future outbreaks.