Lewis histo-blood group α1,3/α1,4 fucose residues may both mediate binding to GII.4 noroviruses

Glycobiology. 2012 Sep;22(9):1163-72. doi: 10.1093/glycob/cws084. Epub 2012 May 15.


Human noroviruses cause recurrent epidemics of gastroenteritis known to be dominated by the clinically important GII.4 genotype which recognizes human Secretor gene-dependent ABH histo-blood group antigens (HBGAs) as attachment factors. There is increasing evidence that GII.4 noroviruses have undergone evolutionary changes to recognize Lewis antigens and non-Secretor saliva. In this study, we have investigated the possibilities of the Lewis α1,3/α1,4 fucoses as mediators of binding of GII.4 noroviruses to Lewis antigens. The study was carried out using molecular dynamics simulations of Lewis type-1 and type-2 chain HBGAs in complex with VA387 P domain dimers in explicit water. Based on the computer simulations, we suggest the possibility of two receptor binding modes for Lewis HBGAs: the "Secretor pose" with the Secretor Fucα1,2 in the binding site and the "Lewis pose" with the Lewis Fucα1,3/α1,4 residues in the binding site. This was further supported by an extensive GlyVicinity analysis of the Protein Data Bank with respect to the occurrence of the Lewis and Secretor poses in complexes of Lewis antigens with lectins and antibodies as well as GII norovirus strains. The Lewis pose can also explain the interactions of GII.4 norovirus strains with Le(x) and SLe(x) structures. Moreover, the present model suggests binding of complex branched polysaccharides, with the Lewis antigens at the nonreducing end, to P domain dimers of GII.4 strains. Our results are relevant for understanding the evolution of norovirus binding specificities and for in silico design of future antiviral therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / chemistry*
  • ABO Blood-Group System / metabolism
  • Amino Acid Sequence
  • Antibodies / chemistry
  • Antibodies / metabolism
  • Binding Sites
  • Carbohydrate Sequence
  • Databases, Protein
  • Fucose / chemistry*
  • Fucose / metabolism
  • Humans
  • Lectins / chemistry
  • Lectins / metabolism
  • Lewis Blood Group Antigens / chemistry*
  • Lewis Blood Group Antigens / metabolism
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Norovirus / chemistry*
  • Norovirus / metabolism
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism
  • Protein Binding
  • Protein Conformation
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism
  • Stereoisomerism
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism
  • Virus Attachment


  • ABO Blood-Group System
  • Antibodies
  • Lectins
  • Lewis Blood Group Antigens
  • Polysaccharides
  • Receptors, Virus
  • Viral Proteins
  • Fucose