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Development of antibodies to pan-coronavirus spike peptides in convalescent COVID-19 patients
medRxiv - Allergy and Immunology Pub Date : 2020-08-22 , DOI: 10.1101/2020.08.20.20178566
Andrii Rabets , Galyna Bila , Roman Grytsko , Markian Samborsky , Yuriy Rebets , Sandor Vari , Quentin Pagneux , Alexandre Barras , Rabah Boukherroub , Sabine Szunerits , Rostyslav Bilyy

Coronaviruses are sharing several protein regions notable the spike protein (S) on their enveloped membrane surface, with the S1 subunit recognizing and binding to the cellular receptor, while the S2 subunit mediates viral and cellular membrane fusion. This similarity opens the question whether infection with one coronavirus will confer resistance to other coronaviruses? Investigating patient serum samples after SARS-CoV-2 infection in cross-reactivity studies of immunogenic peptides from Middle East respiratory syndrome coronavirus (MERS-CoV), we were able to detect the production of antibodies also recognizing MERS virus antigens. The cross-reactive peptide comes from the heptad repeat 2 (HR2) domain of the MERS virus spike protein. Indeed, the peptide of the HR2 domain of the MERS spike protein, previously proven to induce antibodies against MERS-CoV is sharing 74% homology with the corresponding sequence of SARS-CoV-19 virus. Sera samples of 47 convalescent SARS-CoV-2 patients, validated by RT-PCR-negative testes 30 days post-infection, and samples of 40 sera of control patients (not infected with SARS-CoV-2 previously) were used to establish eventual cross-bind reactivity with the MERS peptide antigen. Significantly stronger binding (p<0.0001) was observed for IgG antibodies in convalescent SARS-CoV-2 patients compared to the control group. If used as an antigen, the peptide of the HR2 domain of the MERS spike protein allows discrimination between post-Covid populations from non-infected ones by the presence of antibodies in blood samples. This suggests that polyclonal antibodies established during SARS-CoV-2 infection has the ability to recognize and probably decrease infectiveness of MERS-CoV infections as well as other coronaviruses. The high homology of the spike protein domain suggests in addition that the opposite effect can also be true: coronaviral infections producing cross-reactive antibodies affective against SARS-CoV-19. The collected data prove in addition that despite the core HR2 region being hidden in the native viral conformation, its exposure during cell entry makes it highly immunogenic. Since inhibitory peptides to this region were previously described, this opens new possibilities in fighting coronaviral infections.

中文翻译:

康复期COVID-19患者泛冠状病毒刺突肽抗体的研制

冠状病毒在其被膜表面共享着几个蛋白区域,特别是刺突蛋白(S),其中S1亚基识别并结合到细胞受体上,而S2亚基介导病毒和细胞膜融合。这种相似性提出了一个问题,即一种冠状病毒感染是否会赋予对其他冠状病毒的抗药性?在对来自中东呼吸综合征冠状病毒(MERS-CoV)的免疫原性肽的交叉反应性研究中,对SARS-CoV-2感染后的患者血清样本进行了研究,我们能够检测到也识别MERS病毒抗原的抗体的产生。交叉反应肽来自MERS病毒刺突蛋白的七肽重复序列2(HR2)域。实际上,MERS穗蛋白的HR2结构域的肽,以前被证明能诱导针对MERS-CoV的抗体与SARS-CoV-19病毒的相应序列具有74%的同源性。感染后30天通过RT-PCR阴性睾丸确认的47例康复期SARS-CoV-2患者的血清样本和对照组患者(先前未感染SARS-CoV-2)的40份血清样本用于确定最终与MERS肽抗原的交叉结合反应。与对照组相比,疗养期SARS-CoV-2患者的IgG抗体具有更强的结合力(p <0.0001)。如果用作抗原,MERS穗蛋白的HR2结构域的肽可以通过血液样品中抗体的存在来区分Covid后群体与未感染群体。这表明在SARS-CoV-2感染期间建立的多克隆抗体具有识别并可能降低MERS-CoV感染以及其他冠状病毒感染性的能力。此外,刺突蛋白结构域的高度同源性也表明相反的作用也可以成立:冠状病毒感染产生对SARS-CoV-19有影响的交叉反应抗体。此外,收集到的数据证明,尽管核心HR2区隐藏在天然病毒构象中,但其在细胞进入过程中的暴露使其具有高度免疫原性。由于先前已经描述了对该区域的抑制肽,因此为对抗冠状病毒感染打开了新的可能性。此外,刺突蛋白结构域的高度同源性也表明相反的作用也可以成立:冠状病毒感染产生对SARS-CoV-19有影响的交叉反应抗体。此外,收集到的数据证明,尽管核心HR2区隐藏在天然病毒构象中,但其在细胞进入过程中的暴露使其具有高度免疫原性。由于先前已经描述了对该区域的抑制肽,因此为对抗冠状病毒感染打开了新的可能性。此外,刺突蛋白结构域的高度同源性也表明相反的作用也可以成立:冠状病毒感染产生对SARS-CoV-19有影响的交叉反应抗体。此外,收集到的数据证明,尽管核心HR2区隐藏在天然病毒构象中,但其在细胞进入过程中的暴露使其具有高度免疫原性。由于先前已经描述了对该区域的抑制肽,因此为对抗冠状病毒感染打开了新的可能性。
更新日期:2020-08-23
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