Probing key interactions between SARS-CoV-2 spike and heparan sulfate

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, continues to cause widespread devastation to the global community. The SARS-CoV-2 virion is studded by ∼30 trimeric spike proteins, which themselves play the predominant role in initiating viral invasion by binding to human angiotensin-converting enzyme 2 (hACE2). However, this simple model of spike and hACE2 binding is merely half of the story. All cell surfaces are surrounded by a dense sugary matrix, called the glycocalyx, which is composed of various types of glycoconjugates, including N-linked and O-linked glycoproteins, glycosphingolipids, and proteoglycans.