A group from Molecular Targets Program, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, MD, USA, etc. has reported that Cyanovirin-N binds selectively to SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain (RBD) and blocks infection by SARS-CoV-2.
https://www.pnas.org/doi/full/10.1073/pnas.2214561120
Cyanovirin-N, CV-N, showed inhibitory activity against all tested variants of SARS-CoV-2 (WH-1, D614G, B1.1.7 (Alpha), P.1 (Gamma), B1.351 (Beta), B.1.617.2 (Delta), and B1.1.529 (Omicron)) with EC50 values ranging from 40 nM for Omicron to 180 nM for Alpha.
CV-N bound with good affinity to Spike protein and did not bind to the RBD. In detail, CV-N could bind oligo-mannose at N61, N122, and N234 sites of the S1 domain of Spike protein. Since the glycan at position N234 played important roles in both shielding the RBD and in stabilizing the RBD in the “up” conformation, the specific binding of CV-N to the S1 domain of Spike at 234 might sterically block the RBD binding to ACE2.