A team of researchers led by Rensselaer Polytechnic Institute’s Jonathan S. Dordick, Ph.D., Institute Professor of Chemical and Biological Engineering, has illuminated a new possibility for the treatment and prevention of COVID-19 in research published in Communications Biology.
The team found that suramin, a 100-year-old drug still used for human sleeping sickness that has many other potential applications, inhibits the infection of SARS-CoV-2.
“Suramin binds to the ACE2 and cell surface heparan sulfate binding sites on the receptor binding domain (RBD) of the viral spike (S) protein in vitro,” said Dordick. “Both ACE2 and heparan sulfate help the coronavirus infect cells. Suramin, therefore, shows great promise as a treatment for COVID-19.”
Heparan sulfate and suramin had enhanced preferential binding for the S-protein RBD of the omicron variant, and suramin was most effective against the live SARS-CoV-2 omicron subvariant (B.1.1.529) when compared to wild type and delta (B.1.617.2) subvariants in vitro. Interestingly, it had been shown previously in the literature that suramin inhibits the virus RNA-dependent RNA polymerase, a target for the antiviral agent remdesivir. Thus, the drug’s new S-protein target suggests a broad and independent mechanism of action, which may be an advantage in antiviral therapy.
“Suramin and other polysulfated molecules, which target S-protein binding, should be further explored for their potential to inhibit SARS-CoV-2 infection,” said Dordick. “Importantly, as the SARS-CoV-2 virus continues to evolve, it appears to obtain even greater affinity for target cell heparan sulfate, which makes suramin even more effective in blocking this interaction. This is hypothesized to be the reason suramin is more effective on omicron than on delta or the original (wild-type) S-protein.”
Currently, suramin is not approved in the United States due to toxicity concerns. Further studies may demonstrate the effectiveness of repurposed suramin as a COVID-19 therapeutic or as a post-exposure prophylaxis such as a nasal spray.
Dordick, who is a member of the Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies, was joined in research by Rensselaer’s Robert J. Linhardt, Shirley Xu, Seok-Joon Kwon, Andre L. Rodrigues, Maisha Feroz, Keith Fraser, Peng He, and Fuming Zhang; University of Washington’s Paul S. Kwon; and Korea Research Institute of Bioscience and Biotechnology’s Hanseul Oh and Jung Joo Hong.
Paul S. Kwon et al, Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions, Communications Biology (2023). DOI: 10.1038/s42003-023-04789-z
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