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新型冠状病毒肺炎:发现、诊断和药物研发。

COVID-19: Discovery, diagnostics and drug development.

机构信息

Université de Paris, CRI, INSERM UMR 1149, Department of Hepatology, AP-HP Hôpital Beaujon, Clichy, France.

INSERM, U1052, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL1), CNRS UMR_5286, France.

出版信息

J Hepatol. 2021 Jan;74(1):168-184. doi: 10.1016/j.jhep.2020.09.031. Epub 2020 Oct 8.

Abstract

Coronavirus disease 2019 (COVID-19) started as an epidemic in Wuhan in 2019, and has since become a pandemic. Groups from China identified and sequenced the virus responsible for COVID-19, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and determined that it was a novel coronavirus sharing high sequence identity with bat- and pangolin-derived SARS-like coronaviruses, suggesting a zoonotic origin. SARS-CoV-2 is a member of the Coronaviridae family of enveloped, positive-sense, single-stranded RNA viruses that infect a broad range of vertebrates. The rapid release of the sequence of the virus has enabled the development of diagnostic tools. Additionally, serological tests can now identify individuals who have been infected. SARS-CoV-2 infection is associated with a fatality rate of around 1-3%, which is commonly linked to the development of acute respiratory distress syndrome (ARDS), likely resulting from uncontrolled immune activation, the so called "cytokine storm". Risk factors for mortality include advanced age, obesity, diabetes, and hypertension. Drug repurposing has been used to rapidly identify potential treatments for COVID-19, which could move quickly to phase III. Better knowledge of the virus and its enzymes will aid the development of more potent and specific direct-acting antivirals. In the long term, a vaccine to prevent infection is crucial; however, even if successful, it might not be available before 2021-22. To date, except for intravenous remdesivir and dexamethasone, which have modest effects in moderate to severe COVID-19, no strong clinical evidence supports the efficacy of any other drugs against SARS-CoV-2. The aim of this review is to provide insights on the discovery of SARS-CoV-2, its virology, diagnostic tools, and the ongoing drug discovery effort.

摘要

2019 年,新型冠状病毒病(COVID-19)首先在中国武汉暴发,并迅速蔓延至全球,成为大流行疾病。中国科研团队迅速鉴定并测序了引发 COVID-19 的病毒,将其命名为严重急性呼吸综合征冠状病毒 2(SARS-CoV-2),并发现其与蝙蝠和穿山甲来源的 SARS 样冠状病毒具有高度序列同源性,提示该病毒可能来源于动物。SARS-CoV-2 是冠状病毒科的一种包膜、正链、单链 RNA 病毒,可感染多种脊椎动物。该病毒序列的快速发布使诊断工具得以迅速开发,同时血清学检测也可用于识别既往感染者。SARS-CoV-2 感染的病死率约为 1-3%,通常与急性呼吸窘迫综合征(ARDS)的发生相关,其可能与失控的免疫激活,即所谓的“细胞因子风暴”有关。死亡的危险因素包括高龄、肥胖、糖尿病和高血压。药物重定位已被用于快速鉴定 COVID-19 的潜在治疗药物,这些药物可能很快进入 III 期临床试验。更好地了解病毒及其酶将有助于开发更有效和更具针对性的直接抗病毒药物。从长期来看,预防感染的疫苗至关重要;但即使成功研制出疫苗,也可能要到 2021-22 年才能上市。迄今为止,除了在中重度 COVID-19 中有一定疗效的静脉用瑞德西韦和地塞米松外,没有强有力的临床证据支持任何其他药物对 SARS-CoV-2 的疗效。本文旨在提供 SARS-CoV-2 的发现、病毒学、诊断工具以及正在进行的药物发现工作方面的见解。

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