Laboratory of Molecular Targeted Therapy, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
Biol Pharm Bull. 2024;47(5):917-923. doi: 10.1248/bpb.b23-00639.
The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has devastated public health and the global economy. New variants are continually emerging because of amino acid mutations within the SARS-CoV-2 spike protein. Existing neutralizing antibodies (nAbs) that target the receptor-binding domain (RBD) within the spike protein have been shown to have reduced neutralizing activity against these variants. In particular, the recently expanding omicron subvariants BQ 1.1 and XBB are resistant to nAbs approved for emergency use by the United States Food and Drug Administration. Therefore, it is essential to develop broad nAbs to combat emerging variants. In contrast to the massive accumulation of mutations within the RBD, the S2 subunit remains highly conserved among variants. Therefore, nAbs targeting the S2 region may provide effective cross-protection against novel SARS-CoV-2 variants. Here, we provide a detailed summary of nAbs targeting the S2 subunit: the fusion peptide, stem helix, and heptad repeats 1 and 2. In addition, we provide prospects to solve problems such as the weak neutralizing potency of nAbs targeting the S2 subunit.
全球 2019 年冠状病毒病（COVID-19）大流行是由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的，它破坏了公共卫生和全球经济。由于 SARS-CoV-2 刺突蛋白内的氨基酸突变，新的变体不断出现。针对刺突蛋白受体结合域（RBD）的现有中和抗体（nAb）已被证明对这些变体的中和活性降低。特别是最近不断扩大的奥密克戎亚变体 BQ.1.1 和 XBB 对美国食品和药物管理局批准用于紧急使用的 nAb 具有耐药性。因此，开发广谱 nAb 来对抗新出现的变体至关重要。与 RBD 内大量积累的突变相反，S2 亚基在变体之间保持高度保守。因此，针对 S2 区域的 nAb 可能为新型 SARS-CoV-2 变体提供有效的交叉保护。在这里，我们详细总结了针对 S2 亚基的 nAb：融合肽、茎螺旋和七肽重复 1 和 2。此外，我们提供了解决针对 S2 亚基的 nAb 中和效力弱等问题的前景。
