The potential of exploiting multivalency to design potent, broadspectrum anti-SARS-CoV-2 agents has been recently demonstrated with Abs. Linking IgGs together into an engineered pentameric IgM has shown to not only greatly enhance IgG's viral neutralizing potency (up to 230 fold) but also make it insensitive to a range of known immune evasion mutations. The engineered IgM exhibited high potencies against several SARS-CoV-2 variants, e.g. B.1.1.7 (Alpha), P.1 (Gamma) and B.1.351 (Beta), with in vivo rodent models, and thus had great potential to act as a broad spectrum anti-SARS-CoV-2 agent. The IgM's superior antiviral property over IgG is assigned to its larger size and higher binding valency, allowing it bind/crosslink multiple S-proteins on virion surfaces that is not possible by individual IgGs. The potential of multivalent binding in viral neutralization has been further demonstrated with HIV. HIV is well-known for its ability of evading IgG neutralization. Its low number of envelope protein (Env) trimers (~14 per virion) results in large inter-Env distances, making it impossible for individual IgGs to crosslink neighboring Env proteins. Meanwhile, its unique Env trimer structure with heavy glycan shields also prevents intra-Env crosslinking by IgGs. However, by linking two Fabs together via a rigid DNA spacer and systematically tuning the inter-Fab distance, greatly enhanced anti-HIV potency has been achieved for a Fab dimer that has the correct inter-Fab distance for intra-spike crosslinking. Moreover, an engineered tetravalent DVD antibody (containing four variable-domains) displays 100fold enhanced potency over its component divalent antibody against Crimean-Congo hemorrhagic fever virus. These examples as well as our G13-CRD based antivirals clearly demonstrate that exploiting multivalency is a viable and attractive approach to the development of novel antivirals. While the immune evasion ability of SARS-CoV-2 variants has been almost exclusively considered on the basis of individual Ab-S protein interactions, we believe contributions from multivalency evasion should not be ignored and need to be considered seriously in order to develop more robust antivirals. Compared to others, our GNP-CRD based PNL antivirals have several advantages. First, the GNP scaffold size, shape, and lectin valency and flexibility can be easily tuned to match the virus of interest. Second, lectins can be mass-and cheaply-produced by recombinant bacterial expression without using animals. Third, viral glycosylation is common and viral glycosylation sites are mostly conserved, and thus unlikely to be affected from viral variations. This makes viral glycans a potentially more robust target for developing antivirals than peptide epitopes targeted by most neutralizing Abs. Finally, our PNL antivirals are especially useful against viral infections that lack effective neutralizing Abs, or display Ab-enhanced viral infection (e.g. Dengue, Zika). Therefore, we believe the PNL based antivirals reported here represents a highly attractive, robust and more economical alternative to neutralizing Abs in the fight against a wide range of viral infections.