DC-SIGN-GNP conjugation and specific glycan binding. The ECD retains the tetrameric structure and glycan binding properties of native DC-SIGN, while the monomeric CRD defines glycan binding specificity. CRD binds specifically to mannose or fucose containing glycans found on virus surfaces, including SARS-CoV-2, with low to moderate monovalent affinities (Kds: 0.1-3 mM), while DC-SIGN ECD (containing 4 CRDs) displays augmented binding affinity. Both DC-SIGN ECD and CRD were recombinantly expressed in E. coli. and purified by mannose-affinity columns as confirmed by high resolution mass spectrometry (HRMS, SI, section 2), as reported previously. To facilitate lectin-GNP conjugation, two linker molecules based upon a general structure of lipoic acid-undecyl-(ethylene glycol)-carboxylic acid tetrafluorobenze ester (LA-EG11-TFP) were designed. Both linkers contain three functional domains: an LA group for strong GNP anchoring via chelative Au-S bonding; an EG11 spacer for good flexibility, water solubility and resisting non-specific interactions, and a TPF ester for protein labelling via reacting to a surface free amine (Fig. ). We first prepared linker 1, LA-EG11-Tz-TFP, by reacting LA-EG11-tetrazine with trans-cyclooctyne-EG4-TFP ester (TCO-EG4-TFP) via the rapid tetrazine-TCO copper-free click reaction (SI, Section 3.1). While this reaction was rapid, the LA-EG11-Tz-TFP linker was unstable for long-term storage, even at -20 o C, and gradually degraded over 4 months. We therefore prepared linker 2 (LA-EG11-TFP) by direct esterification of LA-EG11-CO2H with TFP (SI, Section 3.2). Linker 2 was highly stable, showing minimal degradation after storage for 12 months at -20 o C as lyophilized powders.