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SARS-CoV-2 综述及正在进行的临床试验。

A Review of SARS-CoV-2 and the Ongoing Clinical Trials.

机构信息

Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.

出版信息

Int J Mol Sci. 2020 Apr 10;21(7):2657. doi: 10.3390/ijms21072657.

Abstract

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including , a broad-spectrum antiviral drug that interferes with the viral replication, and , the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.

摘要

2019 年新型冠状病毒(2019-nCoV,后命名为 SARS-CoV-2)在中国武汉突然爆发,迅速蔓延为全球大流行,这标志着第三种烈性冠状病毒传入人类社会,不仅影响了医疗保健系统,也影响了全球经济。尽管我们在两次先例后对冠状病毒有了巨大的了解,但仍然缺乏有效的治疗和流行病学控制方法。在本文中,我们简要介绍了 SARS-CoV-2 的流行病学、临床特征和分子特征。我们总结了最初武汉研究中的当前流行病学和临床数据,并强调了 SARS-CoV-2 的几个特征,这些特征使其与 SARS-CoV 和中东呼吸综合征冠状病毒(MERS-CoV)不同,例如疾病表现的高度可变性。我们系统地总结了 COVID-19 大流行爆发后迅速启动的当前临床试验。虽然针对 SARS-CoV-2 基因组特异性疫苗和治疗性抗体的试验正在进行中,但这种解决方案更为长期,因为它们需要对其安全性进行彻底测试。另一方面,重新利用先前设计用于治疗其他病毒感染和疾病的现有治疗药物恰好是应对紧急大流行的唯一实用方法,因为这些药物中的大多数已经过安全性测试。这些药物可分为两类,一类可直接针对病毒复制周期,另一类基于免疫治疗方法,旨在增强先天抗病毒免疫反应或减轻失调的炎症反应引起的损伤。初步的临床研究揭示了几种此类药物的有前途的治疗潜力,包括广谱抗病毒药物,可干扰病毒复制,和抗疟药物,可干扰病毒内体进入途径。我们推测,当前的大流行紧急情况将成为基于大数据分析的更系统药物重新利用设计方法的触发因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5efb/7177898/ffd9916b71de/ijms-21-02657-g001.jpg

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