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针对源自中国武汉的新型冠状病毒在疫情爆发情况下的治疗策略。

Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China.

作者信息

Kruse Robert L

机构信息

Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland, 21287, USA.

出版信息

F1000Res. 2020 Jan 31;9:72. doi: 10.12688/f1000research.22211.2. eCollection 2020.

Abstract

A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain, providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).

摘要

一种源自中国武汉的新型冠状病毒(2019 - nCoV)给全球人口带来了潜在的呼吸道病毒大流行风险。当前的努力集中在对感染者的隔离和检疫上。最终,可能需要一种保护性疫苗来控制疫情,以预防2019 - nCoV感染。虽然应大力推进疫苗研究,但目前尚无针对2019 - nCoV感染后的治疗方法,尽管迫切需要找到帮助这些患者并避免潜在死亡的方案。在此,我回顾了治疗2019 - nCoV感染患者的潜在方案,强调了在此次疫情中开发新的有效治疗方法时速度和及时性的必要性。我考虑了药物重新利用、开发中和单克隆抗体疗法以及针对病毒RNA基因组的寡核苷酸策略等选项,同时强调了这些方法的前景和陷阱。最后,我主张现在采用最快的策略来开发一种治疗方法,这种方法可能对病毒未来可能出现的任何突变都具有抗性。该方案是一种生物制剂,它使用与免疫球蛋白Fc结构域融合的病毒受体血管紧张素转换酶2(ACE2)的可溶性形式来阻断2019 - nCoV的进入,提供一种具有最大广度的中和抗体以避免任何病毒逃逸,同时还有助于招募免疫系统以建立持久免疫力。ACE2 - Fc蛋白的序列已提供给研究人员,使其有可能用于重组蛋白表达系统,以便今天就开始生产药物用于同情用药治疗患者,随后再进行正式的临床试验。这样一种治疗方法可以在未来数月至数年保护性疫苗研发出来并广泛可用之前帮助感染患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8be/7029770/03ef2bc131b5/f1000research-9-24634-g0000.jpg

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