Structural insights into broad anti-spike immune responses
Posted - 28 November 2025
Lectures in Biochemistry visiting speaker
Speaker: Dr. Christopher Barnes
Assistant Professor
Department of Biology and Structural Biology
Stanford University
Date: Monday, December 8th, 2025. 3:00 - 4:00 pm
Location: 231 MSB
Abstract: The ongoing threat of zoonotic coronavirus spillover into humans, exemplified by severe acute respiratory syndrome virus 2 (SARS-CoV-2), underscores the urgent need for pan-coronavirus therapeutics that can be deployed to mitigate future pandemics. Here, we identified monoclonal antibodies from COVID-19 convalescent donors that target conserved epitopes in the Spike glycoprotein, including the highly-conserved S2 domain. S2-directed antibodies exhibited broad cross-reactivity across betacoronaviruses, with fusion peptide-directed antibodies demonstrating orthocoronavirae reactivity. Using cryogenic electron microscopy (cryo-EM) and X-ray crystallography, we determined sub-4 Å structures of antibodies bound to the prefusion-stabilized SARS-CoV-2 S2 protein or peptides, revealing distinct binding poses and contact residues relative to previously described S2-directed antibodies. Additionally, X-ray crystallography studies of the ls.019 Fab in complex with the lower HR2 stalk peptide provides, to our knowledge, the first structural visualization of a human monoclonal antibody engaging this epitope. Together, these findings advance our knowledge of conserved and structurally vulnerable sites within the coronavirus S2 subunit that can guide the development of broad-spectrum antibody therapeutics and vaccines against current and emerging coronaviruses.