Wintjens René, Bifani Amanda Makha, Bifani Pablo
Unit of Microbiology, Bioorganic and Macromolecular Chemistry, Department of Research in Drug Development (RD3), Faculté de Pharmacie, Université Libre de Bruxelles, 1050 Brussels, Belgium.
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, 169857 Singapore.
NPJ Vaccines. 2020 Sep 4;5:81. doi: 10.1038/s41541-020-00237-9. eCollection 2020.
The SARS-CoV-2 outbreak originated in China in late 2019 and has since spread to pandemic proportions. Diagnostics, therapeutics and vaccines are urgently needed. We model the trimeric Spike protein, including flexible loops and all N-glycosylation sites, in order to elucidate accessible epitopes for antibody-based diagnostics, therapeutics and vaccine development. Based on published experimental data, six homogeneous glycosylation patterns and two heterogeneous ones were used for the analysis. The glycan chains alter the accessible surface areas on the S-protein, impeding antibody-antigen recognition. In presence of glycan, epitopes on the S1 subunit, that notably contains the receptor binding domain, remain mostly accessible to antibodies while those present on the S2 subunit are predominantly inaccessible. We identify 28 B-cell epitopes in the Spike structure and group them as non-affected by the glycan cloud versus those which are strongly masked by the glycan cloud, resulting in a list of favourable epitopes as targets for vaccine development, antibody-based therapy and diagnostics.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫情于2019年末在中国爆发，此后已蔓延至大流行程度。迫切需要诊断方法、治疗方法和疫苗。我们对三聚体刺突蛋白进行建模，包括柔性环和所有N-糖基化位点，以阐明基于抗体的诊断、治疗和疫苗开发中可及的表位。基于已发表的实验数据，使用六种均匀糖基化模式和两种异质糖基化模式进行分析。聚糖链改变了S蛋白上的可及表面积，阻碍了抗体-抗原识别。在存在聚糖的情况下，S1亚基上的表位（该亚基显著包含受体结合域）对抗体大多仍可及，而S2亚基上的表位则主要不可及。我们在刺突结构中鉴定出28个B细胞表位，并将它们分为不受聚糖云影响的表位和被聚糖云强烈掩盖的表位，从而得出一系列有利的表位作为疫苗开发、基于抗体的治疗和诊断的靶点。
