重组在促进RNA病毒的进化和潜在流行变体的出现中起着关键作用。一些研究调查了SARS-CoV-2之间的重组发生,但没有探索其对病毒与宿主相互作用的影响。为了从频率和分布方面研究重组的负担,首先在BQ亚变体和正在研究的“ML”(多个谱系)表示的序列中的44230个Omicron序列中探索了重组的发生,使用3seq软件。第二,重组对Spike蛋白与ACE2受体以及中和抗体(nAbs)之间相互作用的影响,使用对接工具进行了分析。在BQ和ML菌株中检测到56.91%和82.20%的重组,分别。它主要发生在刺突和ORF1a基因中。对于BQ重组菌株,对接分析表明,穗与ACE2相互作用强,与nAbs相互作用弱。突变S373P,S375F和T376A构成增强RBD与ACE2相互作用的残基网络。RBD中的13个突变(S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,P494S,Q498R,N501Y,和Y505H)和NTD(Y240H)似乎通过改变与nAb的尖峰相互作用而参与重组体的免疫逃避。总之,这项“计算机模拟”研究表明,重组机制在OmicronBQ和ML变体中很常见。它突出了新的关键突变,这可能与增强与ACE2(F376A)的尖峰结合和从nAbs的逃逸有关(RBD:F376A,D405N,R408S,N440K,S477N,P494S,和Y505H;NTD:Y240H)。我们的发现为制定针对未来SARS-CoV-2波的有效预防和治疗策略提供了丰富的见解。
The
recombination plays a key role in promoting evolution of RNA viruses and emergence of potentially epidemic variants. Some studies investigated the
recombination occurrence among SARS-CoV-2, without exploring its impact on virus-host interaction. In the aim to investigate the burden of
recombination in terms of frequency and distribution, the occurrence of recombination was first explored in 44 230 Omicron sequences among BQ subvariants and the under investigation \"ML\" (Multiple Lineages) denoted sequences, using 3seq software. Second, the
recombination impact on interaction between the Spike protein and ACE2 receptor as well as neutralizing antibodies (nAbs), was analyzed using docking tools.
Recombination was detected in 56.91% and 82.20% of BQ and ML strains, respectively. It took place mainly in spike and ORF1a genes. For BQ recombinant strains, the docking analysis showed that the spike interacted strongly with ACE2 and weakly with nAbs. The mutations S373P, S375F and T376A constitute a residue network that enhances the RBD interaction with ACE2. Thirteen mutations in RBD (S373P, S375F, T376A, D405N, R408S, K417N, N440K, S477N, P494S, Q498R, N501Y, and Y505H) and NTD (Y240H) seem to be implicated in immune evasion of recombinants by altering spike interaction with nAbs. In conclusion, this \"in silico\" study demonstrated that the recombination mechanism is frequent among Omicron BQ and ML variants. It highlights new key mutations, that potentially implicated in enhancement of spike binding to ACE2 (F376A) and escape from nAbs (RBD: F376A, D405N, R408S, N440K, S477N, P494S, and Y505H; NTD: Y240H). Our findings present considerable insights for the elaboration of effective prophylaxis and therapeutic strategies against future SARS-CoV-2 waves.