Small-angle X-ray Scattering (SAXS) enables biological systems to be imaged in an aqueous solution, closer to their natural state. It allowed the researchers to visualize the flexibility of antibodies in solution and show how conformational variability of the antigen-binding regions affects antibody pairing. Unexpectedly, the biophysical flexibility of these antibodies correlates with and can modulate their potency. We recently showed how monoclonal antibodies' rigidity leads to increased sensitivity in the detection of nucleocapsid protein from SARS-CoV-2. We employed SAXS and molecular modeling and show how mAb conformational variability affects antibody pairing with SARS-CoV-2 nucleocapsid protein. We propose that the pairing of rigid antibodies can expedite the development of sensitive and selective antigen-detecting point-of-care lateral flow assay devices, which are key for the early diagnosis of SARS-CoV-2 and other pathogens.
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