The Elusive Coreceptors for the SARS-CoV-2 Spike Protein

Viruses. 2022 Dec 25;15(1):67. doi: 10.3390/v15010067.


Evidence suggests that the N-terminal domain (NTD) of the SARS-CoV-2 spike protein interacts with host coreceptors that participate in viral entry. Resolving the identity of coreceptors has important clinical implications as it may provide the basis for the development of antiviral drugs and vaccine candidates. The majority of characteristic mutations in variants of concern (VOCs) have occurred in the NTD and receptor binding domain (RBD). Unlike the RBD, mutations in the NTD have clustered in the most flexible parts of the spike protein. Many possible coreceptors have been proposed, including various sugars such as gangliosides, sialosides, and heparan sulfate. Protein coreceptors, including neuropilin-1 and leucine-rich repeat containing 15 (LRRC15), are also proposed coreceptors that engage the NTD.

Keywords: COVID-19; LRRC15; N-terminal domain; NRP-1; SARS-CoV-2; leucine rich repeat containing 15; mutations; neuropilin-1; receptor binding domain.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / pharmacology
  • COVID-19*
  • Humans
  • Membrane Proteins
  • Protein Binding
  • Receptors, Virus* / metabolism
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus* / genetics


  • Antiviral Agents
  • LRRC15 protein, human
  • Membrane Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Receptors, Virus