BioAcyl Corp

WIKINDX Resources  

Petitjean, S. J. L., Chen, W., & Koehler, M. (2022). Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection. Nature Communications, 13, 2564. 
Added by: Dr. Enrique Feoli (15/08/2023, 11:35)   Last edited by: Dr. Enrique Feoli (15/08/2023, 11:57)
Resource type: Journal Article
DOI: 10.1038/s41467-022-30313-8
ID no. (ISBN etc.): 2041-1723
BibTeX citation key: Petitjean2022
View all bibliographic details
 Categories: BioAcyl Corp
Creators: Chen, Koehler, Petitjean
Collection: Nature Communications		 Views: 4/341
Abstract
The recent emergence of highly transmissible SARS-CoV-2 variants illustrates the urgent need to better understand the molecular details of the virus binding to its host cell and to develop anti-viral strategies. While many studies focused on the role of the angiotensin-converting enzyme 2 receptor in the infection, others suggest the important role of cell attachment factors such as glycans. Here, we use atomic force microscopy to study these early binding events with the focus on the role of sialic acids (SA). We show that SARS-CoV-2 binds specifically to 9-O-acetylated-SA with a moderate affinity, supporting its role as an attachment factor during virus landing to cell host surfaces. For therapeutic purposes and based on this finding, we have designed novel blocking molecules with various topologies and carrying a controlled number of SA residues, enhancing affinity through a multivalent effect. Inhibition assays show that the AcSA-derived glycoclusters are potent inhibitors of cell binding and infectivity, offering new perspectives in the treatment of SARS-CoV-2 infection., Cell surface attachment factors, such as glycans, play an important role in viral infection. Here, Petitjean et al. show that SARS-CoV-2 specifically binds to 9-Oacetylated sialic acid and have designed novel inhibitors based on multivalent derivatives.
  
Notes
SARS-CoV-2 gains its foothold to the host cell surface first via attachment factors (e.g. sialic acid, heparan sulfate, etc.) and then specific receptors (e.g. angiotensin-converting enzyme 2 (ACE2), neuropilin-1) through interactions with its spike viral glycoprotein (S protein) (Fig. 1a). The S protein assembles into a homotrimer and comprises two functional subunits: the S1, responsible for receptor recognition and S2, that triggers membranes fusion (Fig. 1b). The S1-subunit itself can be divided into the N-terminal domain (NTD) containing the glycan-binding domain (GBD) and the C-terminal domain (CTD) accommodating the receptor-binding domain (RBD) (Fig. 1b). The GBD engages glycoproteins and glycolipids in most CoVs, whereas the RBD binds to the ACE2 receptor.

An external file that holds a picture, illustration, etc. Object name is 41467_2022_30313_Fig1_HTML.jpgSARS-CoV-2 spike protein interacts with both cell surface sialic acids and ACE2 for virus cell entry. The sialic acid family includes many derivatives of the nine-carbon sugar neuraminic acid. The N-acetyl-neuraminic acid (Neu5Ac) and 9-O-acetylated sialic acid (9-AcSA) are presented here. The S glycoprotein is composed of two subunits, S1 and S2, and is commonly represented as a sword-like spike. b Protein structure model of SARS-CoV-2 S protein showing the RBD binding domain for ACE2 receptor on top and the flat, non-sunken sialic acid-binding domain for host cell surface sialic acid-binding (purple circle) (PDB ID: 6VXX). The groove-like, sunken SA-binding domain in other human coronaviruses (HCoV) is highlighted in the brown circle. Created with BioRender.com.

 


Added by: Dr. Enrique Feoli  Last edited by: Dr. Enrique Feoli
WIKINDX 6.12.1 | Total resources: 1703 | Username: -- | Bibliography: WIKINDX Master Bibliography | Style: American Psychological Association (APA) | Time Zone: America/Costa_Rica (-06:00)