To detect pathogens and thus potential danger, antigen presenting cells of our immune system possess a battery of receptors, called pathogen recognition receptors (PRRs), that are dedicated to their surveillance and identification 1 . Among PRRs, C-type lectin receptors (CLRs) are dedicated to the recognition of carbohydrate molecular patterns associated to pathogens, and can then contribute to shape an immune response. This family of receptors shares a common domain, known as the Carbohydrate Recognition Domain (CRD), containing a conserved calcium binding site used for the recognition of carbohydrates. The diverse CLRs differ in size, oligomerization state and signaling pathways, and will therefore have a different impact on the immune system depending on the panels of glycans they recognize . However, not all CLRs are strictly dedicated to immunity and some of them are even expressed in other cell types and tissues such as hepatocytes or endothelial cells from blood capillaries to airway epithelia . These lectin receptors, therefore, have other functions such as physiological clearance mechanisms (e.g. asialoglycoprotein receptors ) and cell adhesion molecules (e.g. selectins ), for example. Some pathogens have found strategies to bypass the role of CLRs in immunity activation and even hijack CLRs for their own benefit during the infection process. Thus, subversion of CLRs has been reported to turn these lectins into alternate receptors or attachment factors, notably by HIV , Ebola virus and SARS-CoV virus , responsible of the severe acute respiratory syndrome (SARS) in 2002. In the context of the 2020 world-scale coronavirus outbreak, we , and others , tested the potential role of several CLRs toward the viral transmission process and found that only two of them, DC-SIGN and L-SIGN (CD209 and CD209L, respectively), are exploited by SARS-CoV-2 to enhance its infection. SARS-CoV-2 can interact with both lectins through its highly glycosylated Spike protein and uses them as anchor points at the cell surface. There is still a debate on the detail of this process: some groups have suggested DC/L-SIGN involvement as direct alternative receptors, others only as promoters of a trans-infection mode, whereby the two CLRs play the role of attachment factors, enabling binding and concentration of viruses onto cell surfaces, before transferring it to its fusion receptor ACE2 on permissive cells along the respiratory tract . DC-SIGN and L-SIGN (also called DC-SIGNR for DC-SIGN Related) have a very high sequence similarity (82% for the whole protein, and up to 72% for the sole Carbohydrate Recognition Domain). Both are tetrameric proteins and bind to mannosylated oligosaccharides . The tetramers have similar, but not identical, topology and dynamics and this impacts on some aspects of their recognition profile of multivalent glycoconjugates . Finally, a major difference between the two lectins is their expression in different cell types and tissues. DC-SIGN is expressed on immature dendritic cells, L-SIGN is expressed in human liver sinusoidal endothelial cells, human lung in type II alveolar cells and in endothelial cells and is co-expressed with ACE2 on respiratory tract cells .