Proteoglycans: a common portal for SARS-CoV-2 and extracellular vesicle uptake

Abstract

As structural components of the glycocalyx, heparan sulfate proteoglycans (HSPGs) are involved in multiple pathophysiological processes at the apex of cell signaling cascades, and as endocytosis receptors for particle structures, such as lipoproteins, extracellular vesicles and enveloped viruses, including SARS-CoV-2. Given their diversity and complex biogenesis regulation, HSPGs remain understudied. Here we compile some of the latest studies focusing on HSPGs as internalizing receptors of extracellular vesicles ("endogenous virus") and SARS-CoV-2 lipid-enclosed particles, and highlight similarities in their biophysical and structural characteristics. Specifically, the similarities in their biogenesis, size and lipid composition may explain a common dependence on HSPGs for efficient cell-surface attachment and uptake. We further discuss the relative complexity of extracellular vesicle composition and the viral mechanisms that evolve towards increased infectivity that complicate therapeutic strategies addressing blockade of their uptake.

Global impact of proteoglycan science on human diseases

“… 123 , 124 It is also established that HS proteoglycans act as internalizing receptors for extracellular vesicles and SARS-CoV-2 lipid-enclosed particles. 125 The similarities in their biogenesis, biophysical property, size, and lipid composition could elucidate a shared dependence on HS proteoglycans for effective cell-surface attachment and uptake. 125 …”

“… 125 The similarities in their biogenesis, biophysical property, size, and lipid composition could elucidate a shared dependence on HS proteoglycans for effective cell-surface attachment and uptake. 125 …”

Myocardial Oedema as a Consequence of Viral Infection and Persistence – a Narrative Review with Focus on COVID-19 and Post COVID Sequelae

“…heparan sulphate, sialic acid [381] Human herpesvirus 1, 6 heparan sulphate, syndecan-1 [382,383] Epstein-Barr virus glycoproteins, hyaluronan synthesis [384,385] Human cytomegalovirus heparan sulphate [386,387] Enteroviruses heparan sulphate, P-selectin glycoprotein ligand-1, sialylated glycan [388][389][390] Adenovirus heparan sulphate, sialic acid [391][392][393] Hepatitis C virus heparan sulphate, syndecan-1 [394,395] SARS-CoV-2 heparan sulphate proteoglycans [223,396] Influenza virus sialic acids, hyaluronan synthesis [391,397]…”

Heparanase‐1 and MMPs in Covid‐19 and non‐Covid‐19 pneumonia

“…However, the viral spike protein must first bind to heparan sulfate on the host cell surface to facilitate attachment and entry into the cell. 1,2 The first barrier to cross is the glycocalyx which is composed of glycosaminoglycans (heparan sulfate [HS] and hyaluronic acid [HA]), proteoglycans (syndecans and glypicans), and adsorbed plasma proteins.…”

“…Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), like other coronaviruses, uses its spike protein to bind to the host cell receptor angiotensin‐converting enzyme 2 (ACE2) and enter the cell. However, the viral spike protein must first bind to heparan sulfate on the host cell surface to facilitate attachment and entry into the cell 1,2 . The first barrier to cross is the glycocalyx which is composed of glycosaminoglycans (heparan sulfate [HS] and hyaluronic acid [HA]), proteoglycans (syndecans and glypicans), and adsorbed plasma proteins.…”