The global Covid-19 pandemic caused by SARS-CoV-2 had a devastating impact on the healthcare systems and economies worldwide. The excess mortality associated with Covd-19 is believed to amount to 18 million from 2020-2021, and tens of millions are suffering from long term physical and mental health problems (i.e. long Covid). To combat this, a number of antiviral strategies that target the viral infection process have been developed. As binding of the viral surface trimeric spike (S) protein to the ACE2 receptor on the host cell surface is essential for infectious SARS-CoV-2 entry into cells, most antivirals and vaccines (including those under development) target this interaction. For example, neutralizing antibodies (Abs) bind to the S protein and block infectious viral entry into cells. However, the emergence of SARS-CoV-2 variants with mutations in the S protein that alter antibody epitopes can allow for evasion of neutralizing Abs induced upon vaccination and/or infection. Each SARS-CoV-2 S-protein trimer is heavily glycosylated with 66 N-linked glycans, consisting of oligomannose, hybrid and complex glycans. Glycosylation plays a critical role in viral pathobiology, which include mediating S-protein folding and stability, camouflaging immunogenic epitopes, facilitating ACE2 binding and viral cell entry. Unlike the frequently changing S protein epitopes targeted by neutralizing Abs, no mutations or alternations of S protein glycosylation sites have been reported across SARS-CoV-2 variants of concern identified by the World Health Organisation (WHO) to date, including the highly mutated Omicron variant (BA.1, BA.4. BA.5, see Supporting Information (SI), Table ). While viral glycans are synthesized by the host cell machinery, they exhibit some unique features that differentiate them from host self-glycans, e.g. a high content of under-processed oligomannoses and high glycan density. These make viral surface glycans an attractive target for developing antivirals. Indeed, a few rare but potent and broadly neutralizing Abs target glycans on HIV. For example, antibody 2G12 displays an unusual domain-exchanged structure that brings two Fabs in close proximity to create an extended glycan binding surface, allowing 2G12 to form strong multivalent interactions with densely packed glycans on the same gp160 trimer spike on the HIV surface. This binding is not possible with conventional Abs: their Fabs are too widely (~15 nm) spaced to allow for simultaneous binding to the same gp160 molecule. Unfortunately, due to low natural immunogenicity, glycantargeting Abs remain rare and to date, no anti-SARS-CoV-2 neutralizing Abs are known to be glycan-targeting. Nevertheless, the success of 2G12 and a few other Abs clearly demonstrates that targeting viral glycans by exploiting multivalency is a viable antiviral strategy.