To enter cells viruses have to fuse their membrane to that of the cells they want to infect. The viruses bind to specific proteins (“receptors”) found on target cells. We use tools in molecular biology (CRISPR-Cas9 genetic screens), protein biochemistry, biophysics, and structural biology (X-ray crystallography and cryo-EM) to identify and then visualize how viruses bind to receptors and infect cells.
Antibodies can prevent viruses from entering cells by (1) blocking attachment to receptors, (2) blocking the conformational changes viral surface proteins undergo to allow for fusion of viral and host cell membranes. Some antibodies act as “decoy receptors” (receptor-mimicking antibodies). The epitopes for antibodies that block conformational changes are usually more conserved but are harder to access because they sit closer to the viral membrane. We isolate from the blood of individuals that have recovered from infections anti-viral monoclonal antibodies. Our goal is to develop cocktails of monoclonal antibodies that can be administered to treat or prevent infection.