论文标题
突变增强了SARS-COV-2感染力
Mutations strengthened SARS-CoV-2 infectivity
论文作者
论文摘要
严重的急性呼吸综合症冠状病毒2（SARS-COV-2）感染力是2019年冠状病毒病（COVID-19）预防和经济重新开放的主要关注点。然而，由于其连续进化，SARS-COV-2感染性的严格测定基本上是不可能的，其中超过13752个单核苷酸多态性（SNP）变体中的六个不同亚型。我们基于代数拓扑来开发一种先进的机器学习算法，以定量评估SARS-COV-2峰值糖蛋白（S蛋白）和宿主血管紧张素转化酶2（ACE2）受体的结合亲和力变化。基于突变诱导的结合亲和力变化，我们揭示了六个SARS-COV-2亚型中有五个已中等或更感染性，而一种亚型却削弱了其感染力。我们发现，根据计算的S蛋白-ACE2结合亲和力的变化，SARS-COV-2比SARS-COV更感染。基于对S蛋白受体结合结构域（RBD）的所有可能3686未来突变的系统评估，我们表明，最有可能将来的突变会使SARS-COV-2更具传染性。结合序列比对，概率分析和结合亲和力计算，我们预测受体结合基序（RBM）上的一些残基，即452、489、500、501和505，有很大的机会突变成更明显的感染性近距离的Covid-19菌株。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is a major concern in coronavirus disease 2019 (COVID-19) prevention and economic reopening. However, rigorous determination of SARS-COV-2 infectivity is essentially impossible owing to its continuous evolution with over 13752 single nucleotide polymorphisms (SNP) variants in six different subtypes. We develop an advanced machine learning algorithm based on the algebraic topology to quantitatively evaluate the binding affinity changes of SARS-CoV-2 spike glycoprotein (S protein) and host angiotensin-converting enzyme 2 (ACE2) receptor following the mutations. Based on mutation-induced binding affinity changes, we reveal that five out of six SARS-CoV-2 subtypes have become either moderately or slightly more infectious, while one subtype has weakened its infectivity. We find that SARS-CoV-2 is slightly more infectious than SARS-CoV according to computed S protein-ACE2 binding affinity changes. Based on a systematic evaluation of all possible 3686 future mutations on the S protein receptor-binding domain (RBD), we show that most likely future mutations will make SARS-CoV-2 more infectious. Combining sequence alignment, probability analysis, and binding affinity calculation, we predict that a few residues on the receptor-binding motif (RBM), i.e., 452, 489, 500, 501, and 505, have very high chances to mutate into significantly more infectious COVID-19 strains.
