SARS-CoV-2 Omicron RBD shows weaker binding affinity than the currently dominant Delta variant to human ACE2
Leyun Wu, Liping Zhou, Mengxia Mo, Tingting Liu, Chengkun Wu, Chunye Gong, Kai Lu, Likun Gong, Weiliang Zhu, Zhijian Xu
Abstract
SARS-coronavirus-2 (SARS-CoV-2) Omicron variant (B.1.1.529) is of great concern to the world due to its multiple mutations that may have an impact on transmissibility and immune evasion. 1 Compared to the wild type (WT), Omicron carries as many as 30 single point mutations, 3 deletion mutation and one insertion mutation on its spike protein. Strikingly, there are 15 mutations observed in the Omicron receptor-binding domain (RBD), 10 of which are in the receptor-binding motif (RBM) that human angiotensin-converting enzyme 2 (ACE2) and most monoclonal antibodies (mAbs) interact directly with. As a comparison, the currently dominant variant Delta (B.1.617.2) has only 2 mutations (L452R and T478K) in its RBM and additional K417N and E484K mutations sometimes. Therefore, Omicron variant may significantly impact the binding affinity to ACE2 and effectiveness of currently available mAbs. Consequently, Omicron mutant has aroused wide concern, many countries have taken measures on entry restrictions to prevent its rapid spread. However, the transmissibility and immune evasion risk of Omicron have not been properly evaluated.