包括C端序列和受体结合基序(RBM)的冠状病毒刺突蛋白的三维混合结构被重塑,能量最小化。Further,蛋白质-蛋白质对接表明,SARS-CoV2Lys457-Pro490的受体结合域(RBD)结合在N末端螺旋附近的ACE2受体表面上,形成宿主-病原体附着。在此绑定接口中,SARS-CoV2比BtRsRaTG13-CoV的其他刺突蛋白显示出紧密的氢键网络,SARS-CoV,BtRsBeta-CoV,BtRsCoV相关,穿山甲CoV(PCoV),人类冠状病毒(hCoV),MERS-CoV(MCov),禽CoV(ACov)和PEDV1-CoV。进一步的研究表明,SARS-CoV2RBDPro322-Thr581,SARS-CoVRBDPro309-Pro575,BtRsRaTG13RBDThr581-Thr323,BtRsBeta-CoVRBDSer311-Thr568,BtRsCoV相关的Arg306-Pro575和PCoVRBDGln319-Ser589的完整此外,亚结构域MCoVRBDGly372-Val616,ACoVRBDGly372-Val616和PEDV1-CoVRBDAla315-Tyr675也结合在ACE2的表面,类似于它们的全长刺突蛋白.B细胞表位作图还确定了主要的抗原决定簇,预测这九个亚结构域在重组疫苗开发中非常有用,可以诱导针对SARS-CoV2刺突蛋白的交叉中和抗体,并抑制其与ACE2的连接。
The three-dimensional hybrid structures of coronavirus spike proteins including the C-terminal sequence and receptor binding motif (RBM) was remodeled and energy minimized. Further, protein-protein docking show that Receptor Binding Domain (RBD) of SARS-CoV 2 Lys457-Pro490 bind on the surface of ACE2 receptor near N-terminal helices to form host-pathogen attachment. In this binding interface, SARS-CoV 2 shows a tight network of hydrogen bonds than other spike proteins from BtRsRaTG13-CoV, SARS-CoV, BtRsBeta-CoV, BtRsCoV-related, Pangolin-CoV (PCoV), human-CoV (hCoV), MERS-CoV (MCoV), Avian-CoV (ACoV) and PEDV1-CoV. Further studies show that subdomains from SARS-CoV 2 RBD Pro322-Thr581, SARS-CoV RBD Pro309-Pro575, BtRsRaTG13 RBD Thr581-Thr323, BtRsBeta-CoV RBD Ser311-Thr568, BtRsCoV-related Arg306-Pro575 and PCoV RBD Gln319-Ser589 show binding conformations with ACE2 like their full-length structures of spike proteins. In addition, the subdomains MCoV RBD Gly372-Val616, ACoV RBD Gly372-Val616 and PEDV1-CoV RBD Ala315-Tyr675 also binds on the surface of ACE2 similar to their full-length spike proteins. The B-Cell epitope mapping also identified main antigenic determinants predicting that these nine subdomains are highly useful in recombinant vaccine development in inducing cross neutralizing antibodies against SARS-CoV 2 spike protein and inhibits its attachment with ACE2.