Mosetti Rosanna, Mancini Tiziana, Bertelà Federica, Macis Salvatore, Luchetti Nicole, Minicozzi Velia, Lupi Stefano, D'Arco Annalisa
Department of Basic and Applied Sciences for Engineering (SBAI), Sapienza University of Rome, Via A. Scarpa 16, 00161, Rome, Italy.
Department of Physics, Sapienza University of Rome, P.le A. Moro 2, 00185, Rome, Italy.
Eur Biophys J. 2025 Jul 21. doi: 10.1007/s00249-025-01782-8.
The global outbreak of COVID-19 pandemic has been accompanied by the emergence of numerous mutated forms of the SARS-CoV-2 virus, exhibiting an increasingly refined capacity to adapt to the human host. The majority of mutations affect viral proteins, particularly the Spike glycoprotein (S), leading to alterations in their physicochemical properties, in secondary structures and biological functions. In the present work, we performed, to the best of our knowledge, the first infrared spectroscopic characterization of monomeric spike glycoprotein subunits 1 (S1) of SARS-CoV-2 Beta variant at pH 7.4, combining the experimental results with Molecular Dynamic simulations, Definition of Secondary Structure of Proteins (DSSP) assignments and hydrophobicity calculations. This integrated approach has yielded valuable insights into the protein secondary structure, hydrophobic behaviour, conformational dynamics, and functional attributes, factors essential for a comprehensive understanding of the viral protein domain. Our results reveal that the SARS-CoV-2 S1 Beta variant is characterized by a secondary structure enriched with antiparallel β-sheets, as consistently supported by both experimental data and computational models. Moreover, a comparative analysis of the experimental results with hydrophobicity calculations indicates that the Beta variant exhibits a slightly more hydrophilic nature relative to the SARS-CoV-2 S1 Wild Type.
新冠疫情在全球爆发的同时，出现了许多严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒的变异形式，其适应人类宿主的能力越来越强。大多数突变影响病毒蛋白，特别是刺突糖蛋白（S），导致其物理化学性质、二级结构和生物学功能发生改变。在本研究中，据我们所知，我们首次对pH 7.4条件下SARS-CoV-2贝塔变异株的单体刺突糖蛋白亚基1（S1）进行了红外光谱表征，并将实验结果与分子动力学模拟、蛋白质二级结构定义（DSSP）归属和疏水性计算相结合。这种综合方法为蛋白质二级结构、疏水行为、构象动力学和功能属性提供了有价值的见解，这些因素对于全面理解病毒蛋白结构域至关重要。我们的结果表明，SARS-CoV-2 S1贝塔变异株的特征是富含反平行β折叠的二级结构，实验数据和计算模型均一致支持这一点。此外，将实验结果与疏水性计算进行对比分析表明，与SARS-CoV-2 S1野生型相比，贝塔变异株表现出略强的亲水性。
