Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China.
Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China.
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DOI：
10.12688/f1000research.22211.2
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发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Kruse, Robert L
中科院分区：
文献类型：
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作者：
Kruse, Robert L
目前的工作重点是控制和隔离受感染的个人。最终，可以通过预防2019-nCoV感染的保护性疫苗来控制疫情。虽然应该大力开展疫苗研究，但目前还没有治疗2019-nCoV感染的疗法，尽管迫切需要找到帮助这些患者并排除潜在死亡的选择。在此，我回顾了治疗2019-nCoV患者的潜在选择，重点是在此次疫情中开发新的有效疗法的速度和时效性的必要性。我考虑了药物再利用的选择，发展中和单克隆抗体治疗，以及针对病毒RNA基因组的寡核苷酸策略，强调了这些方法的希望和陷阱。最后，我主张采取最快的策略来开发一种治疗方法，这种方法可以抵抗病毒未来可能发生的任何突变。该提案是一种生物制剂，利用病毒受体的可溶性版本血管紧张素转换酶2 （ACE2）与免疫球蛋白Fc结构域融合，阻断2019-nCoV的进入，提供最大限度的中和抗体，以避免任何病毒逃逸，同时也有助于招募免疫系统来建立持久的免疫力。ACE2-Fc蛋白的序列已提供给研究人员，允许其在重组蛋白表达系统中使用，以便今天开始生产药物，以治疗有同情心使用的患者，而正式的临床试验稍后进行。这种治疗方法可以在保护性疫苗开发出来并在未来几个月到几年内广泛使用之前帮助受感染的患者。
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).