A group from College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UK, etc. has reported that human surfactant protein D (human SP-D) facilitates SARS-CoV-2 binding and entry in DC-SIGN expressing cells
https://www.frontiersin.org/articles/10.3389/fimmu.2022.960733/full
The ability of a recombinant fragment of human SP-D (rfhSP-D) to mediate the binding of SARS-CoV-2 to DC-SIGN expressing cells was evaluated. HEK 293T cells were transfected with a construct containing a DNA sequence of full-length human DC-SIGN to induce DC-SIGN cell surface expression (DC-HEK cells). To assess the effect of rfhSP-D on pseudotypes binding to DC HEK cells, the DC-HEK cells were challenged with rfhSP-D (20µg/ml) treated SARS-CoV-2 Spike protein-expressing pseudotype. Increased binding (~50%) in the treated samples (DC-HEK + SARS-CoV-2 spike Pseudotypes + rfhSP-D) compared to their untreated counterparts (DC-HEK + SARS-CoV-2 spike Pseudotypes) was observed. Similar experiments were done using THP-1 cells treated with PMA and IL-4 to induce the expression of native DC-SIGN. rfhSP-D treatment was found to increase the binding efficiency of the pseudotypes to the THP-1 cells expressing DC-SIGN by ~25%, compared to the untreated controls.
A blind docking approach was attempted to generate SARS-CoV-2 and DC-SIGN complexes. Analysis of the top ranked docked poses revealed that NTD (N-terminal domain) of spike protein interacted with the CRD domain of DC-SIGN. Tripartite complexes were generated by docking C-SIGN and SP-D with Spike protein. The top two docked poses (C1 and C2) were analysed for intermolecular interactions. In both C1 and C2 complexes, DC-SIGN (CRD) interacted with NTD domain of Spike protein. In C1, there were no molecular interactions between Spike protein and rfhSP-D. In C2, Spike protein interacted with rfhSP-D through RBD.
As a conclusion, it was shown that SP-D interacts with RBD and DC-SIGN interacts with NTD of SARS-CoV-2 spike protein, and also SP-D stabilises DC-SIGN and SARS-CoV-2 spike protein interaction.
