Shirzadeh Maryam, Monhemi Hassan, Eftekhari Mohammad
Departemant of Chemistry, Faculty of Science, University of Neyshabur.
J Mol Struct. 2022 Dec 15;1270:133842. doi: 10.1016/j.molstruc.2022.133842. Epub 2022 Jul 31.
The Omicron variant of SARS-CoV-2 emerged in South African in late 2021. This variant has a large number of mutations, and regarded as fastest-spreading Covid variant. The spike RBD region of SARS-CoV-2 and its interaction with human ACE2 play fundamental role in viral infection and transmission. To explore the reason of fast-spreading properties of Omicron variant, we have modeled the interactions of Omicron RBD and human ACE2 using docking and molecular dynamics simulations. Results show that RBD-ACE2 binding site may drastically relocate with an enlarged interface. The predicted interface has large negative binding energies and shows stable conformation in molecular dynamics simulations. It was found that the interfacial area in Omicron RBD-ACE2 complex is increased up to 40% in comparison to wild-type Sars-Cov-2. Moreover, the number of hydrogen bonds significantly increased up to 80%. The key interacting residues become also very different in Omicron variant. The new binding interface can significantly accommodate R403, as a key RBD residue, near ACE2 surface which leads to two new strong salt bridges. The exploration of the new binding interface can help to understand the reasons of high transmission rate of Omicron.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的奥密克戎变种于2021年末在南非出现。该变种有大量突变，被视为传播速度最快的新冠变种。SARS-CoV-2的刺突受体结合域（RBD）区域及其与人血管紧张素转换酶2（ACE2）的相互作用在病毒感染和传播中起关键作用。为探究奥密克戎变种传播速度快的原因，我们利用对接和分子动力学模拟对奥密克戎RBD与人ACE2的相互作用进行了建模。结果表明，RBD-ACE2结合位点可能会大幅重新定位，界面增大。预测的界面具有较大的负结合能，并且在分子动力学模拟中显示出稳定的构象。研究发现，与野生型Sars-Cov-2相比，奥密克戎RBD-ACE2复合物中的界面面积增加了40%。此外，氢键数量显著增加，增幅高达80%。奥密克戎变种中的关键相互作用残基也有很大不同。新的结合界面可以在ACE2表面附近显著容纳作为RBD关键残基的R403，从而形成两个新的强盐桥。对新结合界面的探索有助于理解奥密克戎高传播率的原因。
