Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31400 Toulouse, France.
Institut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, France.
Viruses. 2022 May 8;14(5):999. doi: 10.3390/v14050999.
This paper presents a molecular characterization of the interaction between the SARS-CoV-2 envelope (E) protein and TLR2. We demonstrated that the E protein, both as a recombinant soluble protein and as a native membrane protein associated with SARS-CoV-2 viral particles, interacts physically with the TLR2 receptor in a specific and dose-dependent manner. Furthermore, we showed that the specific interaction with the TLR2 pathway activates the NF-κB transcription factor and stimulates the production of the CXCL8 inflammatory chemokine. In agreement with the importance of NF-κB in the TLR signaling pathway, we showed that the chemical inhibition of this transcription factor leads to significant inhibition of CXCL8 production, while the blockade of the P38 and ERK1/2 MAP kinases only results in partial CXCL8 inhibition. Overall, our findings propose the envelope (E) protein as a novel molecular target for COVID-19 interventions: either (i) by exploring the therapeutic effect of anti-E blocking/neutralizing antibodies in symptomatic COVID-19 patients, or (ii) as a promising non-spike SARS-CoV-2 antigen candidate for inclusion in the development of next-generation prophylactic vaccines against COVID-19 infection and disease.
本文对 SARS-CoV-2 包膜（E）蛋白与 TLR2 之间的相互作用进行了分子特征分析。我们证明，E 蛋白既能作为重组可溶性蛋白，也能作为与 SARS-CoV-2 病毒颗粒相关的天然膜蛋白，以特定且剂量依赖的方式与 TLR2 受体发生物理相互作用。此外，我们表明，与 TLR2 途径的特异性相互作用会激活 NF-κB 转录因子，并刺激 CXCL8 炎症趋化因子的产生。与 NF-κB 在 TLR 信号通路中的重要性一致，我们表明，该转录因子的化学抑制会导致 CXCL8 产生的显著抑制，而 P38 和 ERK1/2 MAP 激酶的阻断仅导致 CXCL8 的部分抑制。总的来说，我们的研究结果提出包膜（E）蛋白是 COVID-19 干预措施的一个新的分子靶点：（i）通过探索针对有症状 COVID-19 患者的抗 E 阻断/中和抗体的治疗效果，或（ii）作为有希望的非刺突 SARS-CoV-2 抗原候选物，纳入下一代针对 COVID-19 感染和疾病的预防性疫苗的开发。
