Adhikari Puja, Jawad Bahaa, Ching Wai-Yim
Department of Physics and Astronomy, University of Missouri-Kansas City, Kansas City, MO 64110, USA.
College of Applied Sciences, University of Technology, Baghdad 10066, Iraq.
Molecules. 2025 May 6;30(9):2061. doi: 10.3390/molecules30092061.
SARS-CoV-2 remains a severe threat to worldwide public health, particularly as the virus continues to evolve and diversify into variants of concern (VOCs). Among these VOCs, Omicron variants exhibit unique phenotypic traits, such as immune evasion, transmissibility, and severity, due to numerous spike protein mutations and the rapid subvariant evolution. These Omicron subvariants have more than 15 mutations in the receptor-binding domain (RBD), a region of the SARS-CoV-2 spike protein that is important for recognition and binding with the angiotensin-converting enzyme 2 (ACE2) human receptor. To address the impact of these high numbers of Omicron mutations on the binding process, we have developed a novel method to precisely quantify amino acid interactions via the amino acid-amino acid bond pair (AABP). We applied this concept to investigate the interface interactions of the RBD-ACE2 complex in four Omicron Variants (BA.1, BA.2, BA.5, and XBB.1.16) with its Wild Type counterpart. Based on the AABP analysis, we have identified all the sites that are affected by mutation and have provided evidence that unmutated sites are also impacted by mutation. We have calculated that the binding between RBD and ACE2 is strongest in OV BA.1, followed by OV BA.2, WT, OV BA.5, and OV XBB.1.16. We also present the partial charge values for all 311 residues across these five models. Our analysis provides a detailed understanding of changes caused by mutation in each Omicron interface complex.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）仍然是对全球公共卫生的严重威胁，尤其是随着该病毒继续进化并多样化为值得关注的变异株（VOC）。在这些VOC中，由于大量刺突蛋白突变和快速的亚变异株进化，奥密克戎变异株表现出独特的表型特征，如免疫逃逸、传播性和严重性。这些奥密克戎亚变异株在受体结合域（RBD）中有超过15个突变，RBD是SARS-CoV-2刺突蛋白的一个区域，对与人类血管紧张素转换酶2（ACE2）受体的识别和结合很重要。为了研究这些大量的奥密克戎突变对结合过程的影响，我们开发了一种新方法，通过氨基酸-氨基酸键对（AABP）精确量化氨基酸相互作用。我们应用这一概念研究了四种奥密克戎变异株（BA.1、BA.2、BA.5和XBB.1.16）及其野生型对应物中RBD-ACE2复合物的界面相互作用。基于AABP分析，我们确定了所有受突变影响的位点，并提供了未突变位点也受突变影响的证据。我们计算出RBD与ACE2之间的结合在奥密克戎变异株BA.1中最强，其次是奥密克戎变异株BA.2、野生型、奥密克戎变异株BA.5和奥密克戎变异株XBB.1.16。我们还给出了这五个模型中所有311个残基的部分电荷值。我们的分析详细了解了每个奥密克戎界面复合物中突变引起的变化。
