新冠病毒S蛋白RBD突变侵染性增强潜在分子作用机制

Predictive study on the potential molecular mechanism of SARS-CoV-2 spike protein RBD mutation to enhance its infectivity

新冠病毒(SARS-CoV-2)出现越来越多侵染性更强的突变体,比较有代表性的毒株是B.1.351和B.1.617,它们的共同特点是在S蛋白484号位点有氨基酸突变。484号位点是一个与hACE2上的残基K31相互作用的位点。从分子动力学和蛋白质对接的角度入手,通过研究新冠病毒的E484K和E484Q突变,发现与hACE2直接作用的氨基酸残基(A475、N487)间的氢键键长缩短。动力学结果表明,475~489这段氨基酸序列具有高度的活跃性,是一个不应该被忽略的药物设计靶点。可以为开发新冠病毒抑制剂提供新靶点,一定程度上预测新冠病毒未来进化方向,同时也为类似的冠状病毒的突变研究提供新思路。

After the outbreak of SARS-CoV-2,more and more mutants with stronger infectivity appeared.The most representative strains were B.1.351 and B.1.617,which had a common feature of amino acid mutation at spike protein 484 site.Site 484 is a site where interacts with residue K31 on hACE2.From the perspective of molecular dynamics and protein docking,E484K and E484Q mutations of SARS-CoV-2 were investigated,and it was found that the hydrogen bonds between amino acid residues(A475 and N489)that directly interact with hACE2 were shortened due to 484 mutations.Kinetic results also showed that amino acid sequence 475-489 was highly active and should not be neglected as drug design targets.It can provide a new target for the development of SARS-CoV-2 inhibitors,predict the future evolutionary direction of SARS-CoV-2 to a certain extent,and also provide a new idea for the mutation research of similar coronavirus.