Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions

作者：Paul S. Kwon, Shirley Xu, Hanseul Oh, Seok‐Joon Kwon, André L. Rodrigues, Maisha M. Feroz, Keith Fraser, Peng He, Fuming Zhang, Jung Joo Hong, Robert J. Linhardt, Jonathan S. Dordick · 发表于：Communications Biology · 年份：2023 · DOI：10.1038/s42003-023-04789-z · 被引用次数：28 · 研究领域：SARS-CoV-2 and COVID-19 Research、interferon and immune responses、Influenza Virus Research Studies

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.