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  4. A Synthetic Multivalent Lipopeptide Derived from Pam3CSK4 with Irreversible Influenza Inhibition and Immuno-Stimulating Effects
 
research article

A Synthetic Multivalent Lipopeptide Derived from Pam3CSK4 with Irreversible Influenza Inhibition and Immuno-Stimulating Effects

Zhu, Yong  
•
Wei, Lixia  
•
Zwygart, Arnaud Charles-Antoine
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March 4, 2024
Small

The activation of the host adaptive immune system is crucial for eliminating viruses. However, influenza infection often suppresses the innate immune response that precedes adaptive immunity, and the adaptive immune responses are typically delayed. Dendritic cells, serving as professional antigen-presenting cells, have a vital role in initiating the adaptive immune response. In this study, an immuno-stimulating antiviral system (ISAS) is introduced, which is composed of the immuno-stimulating adjuvant lipopeptide Pam3CSK4 that acts as a scaffold onto which it is covalently bound 3 to 4 influenza-inhibiting peptides. The multivalent display of peptides on the scaffold leads to a potent inhibition against H1N1 (EC50 = 20 nM). Importantly, the resulting lipopeptide, Pam3FDA, shows an irreversible inhibition mechanism. The chemical modification of peptides on the scaffold maintains Pam3CSK4's ability to stimulate dendritic cell maturation, thereby rendering Pam3FDA a unique antiviral. This is attributed to its immune activation capability, which also acts in synergy to expedite viral elimination.

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Type
research article
DOI
10.1002/smll.202307709
Web of Science ID

WOS:001174293100001

Author(s)
Zhu, Yong  
Wei, Lixia  
Zwygart, Arnaud Charles-Antoine
Gainza, Pablo  
Khac, Quy Ong  
Olgiati, Francesca  
Kurum, Armand  
Tang, Li  
Correia, Bruno  
Tapparel, Caroline
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Date Issued

2024-03-04

Publisher

Wiley-V C H Verlag Gmbh

Published in
Small
Subjects

Physical Sciences

•

Technology

•

Dendritic Cell

•

Influenza

•

Multivalency

•

Pam3Csk4

•

Virucidal

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LPDI  
SUNMIL  
LBI  
FunderGrant Number

HORIZON EUROPE Marie Sklodowska-Curie Actions

Werner Siemens-Stiftung

CRSII5_180323

Swiss National Science Foundation Synergia Grant

754354

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Available on Infoscience
March 18, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/206571
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