Galectin-3 modulates cellular infectivity and inflammatory response mediated by spike protein of SARS-CoV2

We report that the recombinantly produced galectin-3 (Gal-3) not only reduces the infectivity of a pseudotyped lentivirus expressing SARS-CoV2-S protein i.e., LV(CoV2-S) in the susceptible cells but also dampens the inflammatory response of innate immune cells. Glycan moieties of the CoV2-S protein promote cellular infectivity of LV(CoV2-S). Exogenously added Gal-3, acting via its carbohydrate recognition domain (CRD), prevents LV(CoV2-S) infection of the susceptible cells. Accordingly, Gal-3 mediated LV(CoV2-S) neutralization is inhibited when Gal-3 is pre-incubated with either α-lactose or a single domain antibody specific to the CRD of Gal-3. BMDCs from Gal-3KO as compared to those from WT mice generate significantly higher cytokine response and the exogenously added Gal-3 reduces cytokine levels following stimulation with the derivates of CoV2-S protein. Therefore, modifying the interaction of Gal-3 and glycans of the viral CoV2-S protein might represent a strategy that reduces the infectivity of SARS-CoV2 and mitigates immunopathology caused by the virus infection.