Despite the fact that L-SIGN is known to be the preferential attachment factor for West Nile Virus, there was no report of antagonist development or simply of targeting of L-SIGN in anti-infective strategy before the recent COVID 19 outbreak and the identification of L-SIGN as a potential target together with DC-SIGN. COVID 19 has been associated to hyperactivation of the immune system as a major threat for patient . DC-SIGN is a dendritic cell PRR and it is not yet known whether its engagement by recognition of exogenous ligands could reinforce this hyperactivation. On the contrary, L-SIGN is not involved in the mucosal immune response and colocalizes with ACE2-expressing cells in the lungs. Thus, in the case of SARS-CoV-2, for both reasons above, L-SIGN appears as a more relevant target than DC-SIGN for host-targeted antiviral therapies. We have recently reported a set of C2 triazolemodified mono-and pseudo-di-mannosides that inhibit both DC-SIGN and L-SIGN binding to SARS-CoV-2 spike, up to the low micromolar level . However, all these ligands have more or less the same impact on the two receptors and no selective ligand has yet been described for L-SIGN, which is not too surprising, considering the 72% identity of their respective CRDs . Such selective ligands are needed both as probes of the CLRs' role in viral infections and for development as secure antiadhesive antivirals.