Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions.
Paul S KwonShirley XuHanseul OhSeok-Joon KwonAndre L RodriguesMaisha FerozKeith FraserPeng HeFuming ZhangJung Joo HongRobert J LinhardtJonathan S DordickPublished in: Communications biology (2023)
SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variant (B.1.1.529) when compared to wild type and Delta (B.1.617.2) variants in vitro. These results suggest that inhibition of live virus infection occurs through dual SARS-CoV-2 targets of S-protein binding and previously reported RNA-dependent RNA polymerase inhibition and offers the possibility for this and other polysulfated molecules to be used as potential therapeutic and prophylactic options against COVID-19.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- wild type
- binding protein
- angiotensin ii
- angiotensin converting enzyme
- induced apoptosis
- emergency department
- coronavirus disease
- amino acid
- oxidative stress
- signaling pathway
- endoplasmic reticulum stress
- dna methylation
- small molecule
- cell cycle arrest
- transcription factor
- drug induced