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一种利用无细胞系统快速分布式制造广谱抗病毒格里菲斯菌素以缓解大流行的方法。

An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics.

作者信息

Borhani Shayan G, Levine Max Z, Krumpe Lauren H, Wilson Jennifer, Henrich Curtis J, Oâ Keefe Barry R, Lo Donald, Sittampalam G Sitta, Godfrey Alexander G, Lunsford R Dwayne, Mangalampalli Venkata, Tao Dingyin, LeClair Christopher A, Thole Aaron, Frey Douglas, Swartz James, Rao Govind

出版信息

bioRxiv. 2022 Dec 20:2022.12.19.521044. doi: 10.1101/2022.12.19.521044.

DOI:10.1101/2022.12.19.521044
PMID:36597541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9810220/
Abstract

This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced with consistent purity and potency in less than 24 hours. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics. Efficacy was demonstrated against SARS-CoV-2 and HIV-1 and was nearly identical to that of GRFT expressed . The proposed production process is efficient and can be readily scaled up and deployed anywhere in the world where a viral pathogen might emerge. The current emergence of viral variants has resulted in frequent updating of existing vaccines and loss of efficacy for front-line monoclonal antibody therapies. Proteins such as GRFT with its efficacious and broad virus neutralizing capability provide a compelling pandemic mitigation strategy to promptly suppress viral emergence at the source of an outbreak.

摘要

本研究描述了一种广谱抗病毒蛋白——格里菲斯菌素(GRFT)的无细胞生物制造方法,使其能够在不到24小时内以一致的纯度和效力生产出来。我们展示了使用两个独立的无细胞系统(一个植物系统和一个微生物系统)生产GRFT的过程。使用标准的监管指标验证了格里菲斯菌素的纯度和质量。已证明其对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)和人类免疫缺陷病毒1型(HIV-1)有效,且与表达的GRFT的效力几乎相同。所提出的生产工艺高效,可轻松扩大规模并部署到世界上任何可能出现病毒病原体的地方。当前病毒变体的出现导致现有疫苗频繁更新,一线单克隆抗体疗法失效。像GRFT这样具有有效且广泛的病毒中和能力的蛋白质,为在疫情爆发源头迅速抑制病毒出现提供了极具吸引力的大流行缓解策略。

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1
An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics.一种利用无细胞系统快速分布式制造广谱抗病毒格里菲斯菌素以缓解大流行的方法。
bioRxiv. 2022 Dec 20:2022.12.19.521044. doi: 10.1101/2022.12.19.521044.
2
An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics.利用无细胞系统快速分布式制造广谱抗病毒 Griffithsin 以应对大流行的方法。
N Biotechnol. 2023 Sep 25;76:13-22. doi: 10.1016/j.nbt.2023.04.003. Epub 2023 Apr 11.
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Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.皮下给予广谱抗病毒凝集素 griffithsin 在两种实验室啮齿动物模型中的活性和效果。
Antimicrob Agents Chemother. 2014;58(1):120-7. doi: 10.1128/AAC.01407-13. Epub 2013 Oct 21.
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Griffithsin has antiviral activity against hepatitis C virus.格氏乳香素有抗丙型肝炎病毒的活性。
Antimicrob Agents Chemother. 2011 Nov;55(11):5159-67. doi: 10.1128/AAC.00633-11. Epub 2011 Sep 6.
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The griffithsin dimer is required for high-potency inhibition of HIV-1: evidence for manipulation of the structure of gp120 as part of the griffithsin dimer mechanism.格里菲辛二聚体是高效抑制 HIV-1 所必需的:证据表明,它通过改变 gp120 的结构来发挥作用,这是格里菲辛二聚体机制的一部分。
Antimicrob Agents Chemother. 2013 Aug;57(8):3976-89. doi: 10.1128/AAC.00332-13. Epub 2013 Jun 10.
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Rice endosperm is cost-effective for the production of recombinant griffithsin with potent activity against HIV.水稻胚乳对于生产具有高效抗HIV活性的重组格里菲斯素而言具有成本效益。
Plant Biotechnol J. 2016 Jun;14(6):1427-37. doi: 10.1111/pbi.12507. Epub 2016 Jan 23.
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Technoeconomic Modeling of Plant-Based Griffithsin Manufacturing.基于植物的格里菲斯素制造的技术经济模型
Front Bioeng Biotechnol. 2018 Jul 24;6:102. doi: 10.3389/fbioe.2018.00102. eCollection 2018.
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In vitro Study on Synergistic Interactions Between Free and Encapsulated Q-Griffithsin and Antiretrovirals Against HIV-1 Infection.体外研究游离和包封的 Q-Griffithsin 与抗逆转录病毒药物联合抗 HIV-1 感染的协同作用。
Int J Nanomedicine. 2021 Feb 15;16:1189-1206. doi: 10.2147/IJN.S287310. eCollection 2021.
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Griffithsin binds to the glycosylated proteins (E and prM) of Japanese encephalitis virus and inhibit its infection.格里菲斯素与日本脑炎病毒的糖基化蛋白(E蛋白和prM蛋白)结合,并抑制其感染。
Virus Res. 2016 Apr 2;215:50-4. doi: 10.1016/j.virusres.2016.01.016. Epub 2016 Jan 25.
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Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti-HIV microbicide.格里菲斯菌素是一种有效的HIV进入抑制剂,是抗HIV杀微生物剂的极佳候选物。
J Med Primatol. 2007 Aug;36(4-5):244-53. doi: 10.1111/j.1600-0684.2007.00242.x.

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