In this paper, we report on Man84 (2), the first L-SIGN selective ligand. Despite being structurally similar to the 2-triazole-modified mannosides previously reported as dual DC-SIGN/L-SIGN ligands, Man84 binds to L-SIGN with µM affinity and has a surprising 50-fold selectivity for L-SIGN over DC-SIGN. The structure of the L-SIGN/Man84 complex was obtained by X-ray crystallography and helped to explain the source of this selectivity despite the strong identity context between the two sites. NMR studies allowed to examine the binding process in solution for both lectins, confirming the binding selectivity and highlighting the structural differences between the two complexes. Dimeric constructs bearing two copies of Man84 were also prepared. This low level of multivalency allowed to reach nM affinity for L-SIGN and increased the selectivity up to 3 orders of magnitude against DC-SIGN. Finally, the ability of the divalent constructs to block DC-/L_SIGN mediated infection of host cells by Ebola and SARS-CoV-2 viruses was investigated, revealing that they are powerful inhibitors of the process. Our results are reported below.