The human antibodies that best neutralize the novel coronavirus bind to its spike protein. To develop antibody therapies, the laboratory of Steven Almo, Ph.D., needed to know where the best-neutralizing antibodies bind to the protein. Graduate students Natalia Herrera and Nicholas Morano obtained spike protein by expressing its gene in mammalian cells. The New York Structural Biology Center (NYSBC) then obtained cryo-electron microscopy images of ~50,000 particles of the protein.
Ed Eng (NYSBC) and Jeffrey Bonanno, Ph.D., research assistant professor in Dr. Almo’s lab, used computer programs to rapidly reconstruct those images into a molecular envelope (gray area), allowing the researchers to generate a high-resolution model of the protein’s amino-acid strands (represented as blue, red, and green ribbons). Of greatest interest in this structural model of a spike protein is the top part: the “receptor-binding domain” that latches onto the ACE2 receptors of human cells and is targeted by neutralizing antibodies.