SARS-CoV-2刺突糖蛋白突变体与血管紧张素转化酶2结合的热点残基分析

Analysis of Effects of Spike Hotspot Residues on Binding Stability of SARS-CoV-2 Variants with ACE2

严重急性呼吸综合征冠状病毒2(severe scute respiratory syndrome coronavirus 2,SARS-CoV-2)的刺突糖蛋白(spike glycoprotein,S protein)通过其受体结构域(receptor binding domain,RBD)识别并结合宿主细胞表面受体血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2),但S蛋白的突变对其与受体相互作用的影响尚不清楚。本研究通过S蛋白与ACE2的分子对接和蛋白质结合分析发现,相比野生型,501Y和B.1.617谱系与ACE2的结合更稳定,其中501Y.V1突变体与ACE2的结合最稳定;结合界面上RBD中18%的氨基酸突变可以增强S蛋白与受体结合的稳定性。S蛋白突变体与受体的结合信息将对中和抗体和疫苗的设计有所助益。

The spike glycoprotein(S protein)on the surface of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)recognizes and binds to the host cell surface receptor angiotensin-converting enzyme 2(ACE2)through its receptor binding domain(RBD),but the effect of mutations in the S protein RBD on its interaction with the receptor is unclear.Through molecular docking and protein binding analysis of S protein and ACE2,this study found that,compared with the wild-type,the strains of both 501Y and B.1.617 lineages displayed more stable receptor-binding ability.Among the variants,501Y.V1 was proved to be the most stable strain.At the RBD-ACE2 binding interface,18%of single amino acid mutations in RBD could enhance the stability of the RBD-ACE2 complex.Knowing about the receptor-binding information of SARS-CoV-2 spike variants would be helpful in designing neutralizing antibodies and vaccines against the viral infection.