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Poly‐ l‐ lysine Glycoconjugates Inhibit DC‐SIGN‐mediated Attachment of Pandemic Viruses
Author(s) -
Cramer Jonathan,
Aliu Butrint,
Jiang Xiaohua,
Sharpe Timothy,
Pang Lijuan,
Hadorn Adrian,
Rabbani Said,
Ernst Beat
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100348
Subject(s) - internalization , glycoconjugate , dc sign , glycoprotein , viral envelope , entry inhibitor , viral matrix protein , viral entry , chemistry , context (archaeology) , lectin , receptor , virus , microbiology and biotechnology , biochemistry , virology , biology , viral replication , immunology , dendritic cell , paleontology , antigen
The C‐type lectin receptor DC‐SIGN mediates interactions with envelope glycoproteins of many viruses such as SARS‐CoV‐2, ebola, and HIV and contributes to virus internalization and dissemination. In the context of the recent SARS‐CoV‐2 pandemic, involvement of DC‐SIGN has been linked to severe cases of COVID‐19. Inhibition of the interaction between DC‐SIGN and viral glycoproteins has the potential to generate broad spectrum antiviral agents. Here, we demonstrate that mannose‐functionalized poly‐ l ‐lysine glycoconjugates efficiently inhibit the attachment of viral glycoproteins to DC‐SIGN‐presenting cells with picomolar affinity. Treatment of these cells leads to prolonged receptor internalization and inhibition of virus binding for up to 6 h. Furthermore, the polymers are fully bio‐compatible and readily cleared by target cells. The thermodynamic analysis of the multivalent interactions reveals enhanced enthalpy‐driven affinities and promising perspectives for the future development of multivalent therapeutics.