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针对新型冠状病毒 SARS-CoV-2 的基于肽的亚单位疫苗设计。

Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2.

机构信息

Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong, 793022, India; Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.

Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, Yokohama, Kanagawa, 230-0045, Japan.

出版信息

Microb Pathog. 2020 Aug;145:104236. doi: 10.1016/j.micpath.2020.104236. Epub 2020 May 4.

Abstract

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.

摘要

新型冠状病毒病(COVID-19)是一种新发传染病,最初在中国武汉报告,随后在全球范围内传播。由于缺乏抗病毒或免疫调节治疗方法,该疾病的传播速度令人震惊。在已经实施封锁的地方,COVID-19 再次爆发的可能性也在增加。因此,控制 COVID-19,疫苗可能是比药物更好的选择。一种基于 mRNA 的抗 COVID-19 候选疫苗已进入 1 期临床试验。然而,其疗效和效力尚待评估和验证。由于疫苗的失败率很高,因此作为替代方案,我们提出了一种针对 COVID-19 的新型、设计的多肽亚单位表位疫苗。重组疫苗构建体由佐剂、细胞毒性 T 淋巴细胞(CTL)、辅助性 T 淋巴细胞(HTL)和 B 细胞表位通过接头连接而成。计算数据表明,该疫苗无毒性、无变应原性、热稳定性好,能够引发体液和细胞介导的免疫反应。通过分子动力学模拟研究验证了疫苗构建体的稳定性。这种独特的疫苗由来自三种蛋白的 33 个高度抗原性表位组成,这些表位在宿主受体识别、病毒进入和致病性方面发挥着重要作用。我们主张应将该疫苗作为公共卫生的重点紧急合成和测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e38/7196559/f12343e5defb/gr1_lrg.jpg

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