Enhancing RBD exposure and S1 shedding by an extremely conserved SARS-CoV-2 NTD epitope

作者：Qianhui Zhu, Pan Liu, Shuo Liu, Can Yue, Xiangxi Wang · 发表于：Signal Transduction and Targeted Therapy · 年份：2024 · DOI：10.1038/s41392-024-01940-y · 被引用次数：7 · 研究领域：SARS-CoV-2 and COVID-19 Research、Virus-based gene therapy research、Bacteriophages and microbial interactions

Multiple waves of outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have resulted in unprecedented public health and socioeconomic crises. After 4 years of primary as well as breakthrough infections and under the increased immune pressure exerted by vaccination, SARS-CoV-2 has evolved into multiple variants that displayed either enhanced transmissibility or immune escape properties. The currently dominant variant, BA.2.86 sublineages, with over 35 mutations in Spike (S), showed higher immune evasion and formed a distinct BA.2.86 sub-lineage branch via phylogenetic analysis of the primary sequences of S. 1 To mitigate the spread of epidemic and impact on public health, a large number of monoclonal antibodies have been developed and deployed rapidly. The class I anti-RBD NAbs like DXP-604 and LY-CoV016, which bind RBD “up” conformation, can block ACE2 binding and have strong neutralizing activity. 2 However, RBD is also a domain with a very high mutation frequency, rendering most clinically authorized anti-RBD NAbs ineffective against new BA.2.86 sublineages harboring such mutations. 3 Among the four classes of anti-NTD NAbs (α, β, γ, δ), 2 the first three classes antibodies have been evaded due to antigenic changes. Here, we found that two δ-class antibodies, XG2v046 and XGv280, which recognize the conserved epitope of NTD and can enhance RBD exposure and S1 shedding by promoting RBD to assume “up” conformation as a neutralizing mechanism, have broad-sp...