Heparan sulfate proteoglycans as attachment factor for SARS-CoV-2.
Lin LiuPradeep ChopraXiuru LiKim M BouwmanStephen Mark TompkinsMargreet A WolfertRobert P de VriesGeert-Jan BoonsPublished in: bioRxiv : the preprint server for biology (2021)
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing an unprecedented global pandemic demanding the urgent development of therapeutic strategies. Microarray binding experiments using an extensive heparan sulfate (HS) oligosaccharide library showed that the receptor binding domain (RBD) of the spike of SARS-CoV-2 can bind HS in a length- and sequence-dependent manner. Hexa- and octa-saccharides composed of IdoA2S-GlcNS6S repeating units were identified as optimal ligands. Surface plasma resonance (SPR) showed the SARS-CoV-2 spike protein binds with much higher affinity to heparin (KD = 55 nM) compared to the RBD (KD = 1 uM) alone. We also found that heparin does not interfere in angiotensin-converting enzyme 2 (ACE2) binding or proteolytic processing of the spike. Our data supports a model in which HS functions as the point of initial attachment for SARS-CoV-2 infection. Tissue staining studies using biologically relevant tissues indicate that heparan sulfate proteoglycan (HSPG) is a critical attachment factor for the virus. Collectively, our results highlight the potential of using HS oligosaccharides as a therapeutic agent by inhibiting SARS-CoV-2 binding to target cells.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- angiotensin converting enzyme
- angiotensin ii
- binding protein
- venous thromboembolism
- induced apoptosis
- gene expression
- signaling pathway
- dna binding
- photodynamic therapy
- amino acid
- risk assessment
- growth factor
- big data
- climate change
- machine learning
- cell proliferation
- transcription factor
- oxidative stress
- quantum dots
- flow cytometry
- data analysis
- protein protein
- cell death