Poly-L-lysine Glycoconjugates Inhibit DC-SIGN-mediated Attachment of Pandemic Viruses

ChemMedChem. 2021 Jun 1. doi: 10.1002/cmdc.202100348. Online ahead of print.ABSTRACTThe 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 entropy-driven affinities and promising perspectives for the future development of multivalent therapeutics.PMID:34061468 | DOI:10.1002/cmdc.202100348
Source: ChemMedChem - Category: Chemistry Authors: Source Type: research