SARS-CoV-2 Spike protein–Fc gamma receptor interface (Spike–FcγR interface)

The SARS-CoV-2 Spike protein–Fc gamma receptor (FcγR) interface is a multi-component molecular complex formed when antibodies bind to the viral Spike protein and subsequently engage Fc receptors on the surface of immune cells. This interface is a primary driver of the host's immune effector response, facilitating the elimination of the virus through mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) [1][2]. Beyond viral clearance, these interactions play a dual role in disease progression; while they are essential for protection, aberrant FcγR signaling can trigger hyper-inflammatory responses and potentially mediate antibody-dependent enhancement (ADE), where non-neutralizing antibodies facilitate viral entry into myeloid cells [3][4]. In the context of drug development, this interface is a critical target for engineering monoclonal antibodies, where the Fc region is often modified (e.g., LALA or YTE mutations) to either enhance protective effector functions, extend half-life via FcRn interaction, or abolish pro-inflammatory risks [5][6]. Consequently, this interface serves as a pivotal checkpoint for determining the balance between protective immunity and immunopathology in COVID-19 [7]. Sources: [1] https://www.nature.com/articles/s41577-020-00448-3; [2] https://pubmed.ncbi.nlm.nih.gov/33505050/; [3] https://www.science.org/doi/10.1126/science.abi7943; [4] https://www.nature.com/articles/s41586-020-2538-8; [5] https://www.nature.com/articles/s41587-020-0662-0; [6] https://www.frontiersin.org/articles/10.3389/fimmu.2019.01296/full; [7] https://www.nature.com/articles/s41577-020-0311-8.

Other names

SARS-CoV-2 Spike-FcR complexSpike-IgG-FcγR axisFc-mediated immune interfaceSpike-Fc receptor interactionSARS-CoV-2 Spike-antibody-FcγR complex

Modulation of Fc-mediated effector functions (ADCC/ADCP) and viral neutralization through the binding of the Spike protein and subsequent recruitment of Fc gamma receptors on immune cells.