Multivalent lectin-glycan interactions are widespread and play a key role in pathogen recognition and immune regulation. Besides, lectins have also shown to display useful antiviral activities by binding to viral surface glycans. However, some lectins, including a dendritic cell surface tetrameric lectin, DC-SIGN, have been shown to bind and transmit SARS-CoV-2 to target cells, albeit less effective than ACE2. Therefore, we propose a new polyvalent nano-lectin (PNL) antiviral strategy by displaying tetrameric DC-SIGN extracellular domain (ECD) or its monomeric carbohydrate-recognition-domain (CRD) polyvalently and flexibly on gold nanoparticle (GNP) scaffolds. We hypothesize that the flexibly displayed ECDs or CRDs in each PNL will be able to adjust their relative positions, allowing for strong multivalent binding to glycans on viral S proteins to inhibit viral entry (see Fig. ). Moreover, PNLs may bind to glycans from different domains on the same trimeric S protein (i.e. intra-spike crosslinking) and/or in between neighboring S-proteins on virion particles (inter-spike crosslinking). Such binding may interrupt S protein conformational changes that are essential for virus entry into cells. A GNP scaffold is chosen here because of excellent biocompatibility, low-/non-cytotoxicity, tuneable size, and robust gold-thiol chemistry for convenient surface modification and bioconjugation. In addition, GNP glycan or peptide conjugates have been successfully used to detect SARS-COV-2 virus or antiviral IgG Abs, respectively. Hence, the key PNL parameters (e.g. size, lectin valency and flexibility) required for potent virus neutralization can be readily tuned.