Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies

Nature. 2021 Oct;598(7880):342-347. doi: 10.1038/s41586-021-03925-1. Epub 2021 Aug 31.


SARS-CoV-2 infection-which involves both cell attachment and membrane fusion-relies on the angiotensin-converting enzyme 2 (ACE2) receptor, which is paradoxically found at low levels in the respiratory tract1-3, suggesting that there may be additional mechanisms facilitating infection. Here we show that C-type lectin receptors, DC-SIGN, L-SIGN and the sialic acid-binding immunoglobulin-like lectin 1 (SIGLEC1) function as attachment receptors by enhancing ACE2-mediated infection and modulating the neutralizing activity of different classes of spike-specific antibodies. Antibodies to the amino-terminal domain or to the conserved site at the base of the receptor-binding domain, while poorly neutralizing infection of ACE2-overexpressing cells, effectively block lectin-facilitated infection. Conversely, antibodies to the receptor binding motif, while potently neutralizing infection of ACE2-overexpressing cells, poorly neutralize infection of cells expressing DC-SIGN or L-SIGN and trigger fusogenic rearrangement of the spike, promoting cell-to-cell fusion. Collectively, these findings identify a lectin-dependent pathway that enhances ACE2-dependent infection by SARS-CoV-2 and reveal distinct mechanisms of neutralization by different classes of spike-specific antibodies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Cell Adhesion Molecules / metabolism
  • Cell Fusion
  • Cell Line
  • Cricetinae
  • Female
  • Humans
  • Lectins / immunology
  • Lectins / metabolism*
  • Lectins, C-Type / metabolism
  • Membrane Fusion
  • Receptors, Cell Surface / metabolism
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / metabolism*
  • SARS-CoV-2 / pathogenicity*
  • Sialic Acid Binding Ig-like Lectin 1 / metabolism
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism


  • Antibodies, Neutralizing
  • CLEC4M protein, human
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins
  • Lectins, C-Type
  • Receptors, Cell Surface
  • SIGLEC1 protein, human
  • Sialic Acid Binding Ig-like Lectin 1
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2