Khare Sangeeta, Azevedo Marli, Parajuli Pravin, Gokulan Kuppan
Division of Microbiology, National Center for Toxicological Research, United States-Food and Drug Administration, Jefferson, AR, United States.
Front Artif Intell. 2021 Mar 25;4:630955. doi: 10.3389/frai.2021.630955. eCollection 2021.
COVID-19, the illness caused by the SARS-CoV-2 virus, is now a worldwide pandemic with mortality in hundreds of thousands as infections continue to increase. Containing the spread of this viral infection and decreasing the mortality rate is a major challenge. Identifying appropriate antigenic epitopes from the viral proteins is a very important task for vaccine production and the development of diagnostic kits and antibody therapy. A novel antigenic epitope would be specific to the SARS-CoV-2 virus and can distinguish infections caused by common cold viruses. In this study two approaches are employed to identify both continuous and conformational B-cell antigenic epitopes. To achieve this goal, we modeled a complete structure of the receptor binding domain (RBD) of the spike protein using recently deposited coordinates (6vxx, 6vsb, and 6w41) in the protein data bank. In addition, we also modeled the RBD-ACE2 receptor complex for SARS-CoV-2 using the SARS-CoV RBD-ACE2 complex (3D0J) as a reference model. Finally, structure based predicted antigenic epitopes were compared to the ACE2 binding region of RBD of SARS-CoV-2. The identified conformational epitopes show overlaps with the ACE2-receptor binding region of the RBD of SARS-CoV-2. Strategies defined in the current study identified novel antigenic epitope that is specific to the SARS-CoV-2 virus. Integrating such approach in the diagnosis can distinguish infections caused by common cold viruses from SARS-CoV-2 virus.
新型冠状病毒肺炎(COVID-19)是由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的疾病,随着感染人数持续增加,现已成为全球大流行疾病,导致数十万人死亡。控制这种病毒感染的传播并降低死亡率是一项重大挑战。从病毒蛋白中识别合适的抗原表位对于疫苗生产、诊断试剂盒的开发以及抗体治疗来说是一项非常重要的任务。一种新型抗原表位将对SARS-CoV-2病毒具有特异性,并且能够区分由普通感冒病毒引起的感染。在本研究中,采用了两种方法来识别连续和构象性B细胞抗原表位。为实现这一目标,我们利用最近存入蛋白质数据库的坐标(6vxx、6vsb和6w41)对刺突蛋白受体结合域(RBD)的完整结构进行建模。此外,我们还以SARS-CoV RBD-ACE2复合物(3D0J)作为参考模型,对SARS-CoV-2的RBD-ACE2受体复合物进行建模。最后,将基于结构预测的抗原表位与SARS-CoV-2 RBD的ACE2结合区域进行比较。所识别的构象表位与SARS-CoV-2 RBD的ACE2受体结合区域存在重叠。本研究中定义的策略识别出了对SARS-CoV-2病毒具有特异性的新型抗原表位。将这种方法整合到诊断中可以区分普通感冒病毒引起的感染和SARS-CoV-2病毒引起的感染。