Chakraborty Chiranjib, Mallick Bidyut, Bhattacharya Manojit, Byrareddy Siddappa N
Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, West Bengal 700126, India.
Department of Applied Sciences and Humanities, Galgotias College of Engineering and Technology, Knowledge Park-II, Greater Noida 201306, India.
J Genet Eng Biotechnol. 2024 Mar;22(1):100347. doi: 10.1016/j.jgeb.2023.100347. Epub 2024 Jan 22.
Emergences of SARS-CoV-2 variants have made the pandemic more critical. Toll-like receptor 4 (TLR4) recognizes the molecular patterns of pathogens and activates the production of proinflammatory cytokines to restrain the infection. We have identified a molecular basis of interaction between the Spike and TLR4 of SARS-CoV-2 and its present and past VOCs (variant- of concern) through in silico analysis. The interaction of wild type Spike with TLR4 showed 15 number hydrogen bonds formation. Similarly, the Alpha variants' Spike with the TLR4 has illustrated that 14 hydrogen bonds participated in the interaction. However, the Delta Spike and TLR4 interaction interface showed that 17 hydrogen bonds were formed during the interaction. Furthermore, Omicron S-glycoprotein and TLR4 interaction interface was depicted (interaction score: -170.3), and 16 hydrogen bonds were found to have been formed in the interaction. Omicron S-glycoprotein shows stronger binding affinity with the TLR4 than wild type, Alpha, and Delta variants. Similarly, the Alpha Spike shows higher binding affinity with TLR4 than the wild type and Delta variant. Now, it is an open question of the molecular basis of the interaction of Spike and TLR4 and the activated downstream signaling events of TLR4 for SARS-CoV-2 and its variants.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现使疫情变得更加严峻。Toll样受体4（TLR4）识别病原体的分子模式并激活促炎细胞因子的产生以抑制感染。我们通过计算机模拟分析确定了SARS-CoV-2及其当前和过去的关注变体（VOC）的刺突蛋白与TLR4之间相互作用的分子基础。野生型刺突蛋白与TLR4的相互作用显示形成了15个氢键。同样，α变体的刺突蛋白与TLR4的相互作用表明有14个氢键参与其中。然而，δ变体的刺突蛋白与TLR4的相互作用界面显示在相互作用过程中形成了17个氢键。此外，还描绘了奥密克戎S糖蛋白与TLR4的相互作用界面（相互作用得分：-170.3），并且发现在相互作用中形成了16个氢键。奥密克戎S糖蛋白与TLR4的结合亲和力比野生型、α和δ变体更强。同样，α变体的刺突蛋白与TLR4的结合亲和力比野生型和δ变体更高。现在，SARS-CoV-2及其变体的刺突蛋白与TLR4相互作用的分子基础以及TLR4激活的下游信号事件仍是一个悬而未决的问题。
