Poly-l-lysine Glycoconjugates Inhibit DC-SIGN-mediated Attachment of Pandemic Viruses.
ChemMedChem
; 16(15): 2345-2353, 2021 08 05.
Article
in English
| MEDLINE | ID: covidwho-1248684
ABSTRACT
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 6â
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Glycoconjugates
/
Cell Adhesion Molecules
/
Receptors, Cell Surface
/
Lectins, C-Type
/
Virus Attachment
Limits:
Humans
Language:
English
Journal:
ChemMedChem
Journal subject:
Pharmacology
/
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
Cmdc.202100348
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