Gal-3BP in Viral Infections: An Emerging Role in Severe Acute Respiratory Syndrome Coronavirus 2

Galectin-3 binding protein (Gal-3BP) is a multifunctional glycoprotein involved in cell-cell and cell-matrix interactions known to be upregulated in cancer and various viral infections, including HIV-1, HCV, and SARS-CoV-2, with a key role in regulating the antiviral immune response. Studies have identified a direct correlation between circulating levels of Gal-3BP and the severity of disease and/or disease progression for some viral infections, including SARS-CoV-2, suggesting a role of Gal-3BP in these processes. Due to Gal-3BP's complex biology, the molecular mechanisms underlying its role in viral diseases have been only partially clarified. Gal-3BP induces the expression of interferons (IFNs) and proinflammatory cytokines, including interleukin-6 (IL-6), mainly interacting with galectin-3, targeting the TNF receptor-associated factors (TRAF-6 and TRAF-3) complex, thus having a putative role in the modulation of TGF-beta signaling. In addition, an antiviral activity of Gal-3BP has been ascribed to a direct interaction of the protein with virus components. In this review, we explored the role of Gal-3BP in viral infections and the relationship between Gal-3BP upregulation and disease severity and progression, mainly focusing on SARS-CoV-2. Augmented knowledge of Gal-3BP's role in virus infections can be useful to evaluate its possible use as a prognostic biomarker and as a putative target to block or attenuate severe disease.