Combining small antibodies called nanobodies into single molecules to block the novel coronavirus may be more effective than targeting it with conventional antibodies or single nanobodies, according to a new study. These multivalent nanobodies "are substantially better in neutralizing viruses" and preventing them from breaking into cells, study leaders Florian Schmidt and Paul-Albert König of the University of Bonn told Reuters. The fused nanobodies work synergistically, "so that the outcome is better than just the sum of the two responses," they said. "For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies," the researchers and their colleagues explained in a report in Science. They generated four neutralizing nanobodies that target the receptor-binding domain of the SARS-CoV-2 spike protein and identified two distinct binding epitopes. "Based on the structures, we engineered multivalent nanobodies with more than 100-fold improved neutralizing activity than monovalent nanobodies," they reported. Because the nanobody constructs target multiple sites on the coronavirus, they make it harder for the pathogen to develop mutations that render treatment ineffective, the research team says. While they saw plenty of mutations that allowed the coronavirus to "escape" the effect of a single nanobody, "we did not find any escape mutants that were able to replicate in the presence of those nanobodies that target two different surfaces at the same time," Schmidt and König said. A spin-off company of the University of Bonn, called DiosCURE, expects to start testing the combined nanobody molecules in people later this year. —Reuters Staff Source
