Antigenic landscape of a highly mutated SARS-CoV-2 spike in ongoing viral evolution.

BA.2.87.1’s heavily NTD-remodeled SARS-CoV-2 Spike retains overall structure and pseudovirus infectivity despite large deletions, but loses heme-metabolite interaction and antibody engagement.

• Why it matters: Immune-experienced populations drive SARS-CoV-2 evolution, yet how extensive NTD remodeling alters antigenicity and antibody recognition remains unclear.
• What they did: Structural and binding analyses assessed NTD flexibility and heme-metabolite interaction, while pseudovirus infectivity and human convalescent antibody binding were tested alongside 33 NTD mutations.
• The result: NTD conformational changes and 33 mutations compromised human convalescent antibodies’ ability to engage the domain, reducing neutralizing capacity and suggesting BA.2.87.1-like variants may escape preexisting NTD-targeting antibodies.