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瑞德西韦治疗 COVID-19 及其他病毒性疾病。

Remdesivir against COVID-19 and Other Viral Diseases.

机构信息

Department I of Internal Medicine, Division of Infectious Diseases, University of Cologne, Cologne, Germany

Faculty of Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

出版信息

Clin Microbiol Rev. 2020 Oct 14;34(1). doi: 10.1128/CMR.00162-20. Print 2020 Dec 16.

Abstract

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. , remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.

摘要

全球的患者和医生都面临着由持续的严重急性呼吸窘迫综合征冠状病毒 2 型(SARS-CoV-2)大流行所带来的巨大的医疗保健危害。瑞德西韦(GS-5734)是首个批准用于治疗严重 2019 年冠状病毒病(COVID-19)的药物。它是一种新型核苷类似物,对包括埃博拉病毒(EBOV)和呼吸道病原体中东呼吸综合征冠状病毒(MERS-CoV)、严重急性呼吸综合征冠状病毒(SARS-CoV)和 SARS-CoV-2 在内的 RNA 病毒具有广泛的抗病毒活性谱。该药物于 2016 年首次被描述,最初是从旨在针对新兴致病性 RNA 病毒的小分子抗病毒文库中衍生出来的。在 EBOV、MERS-CoV、SARS-CoV 和 SARS-CoV-2 感染的动物模型中,瑞德西韦表现出治疗和预防作用。然而,该物质在埃博拉病毒病(EVD)的临床试验中失败,在中期分析中,它不如研究性单克隆抗体。由于该研究中没有安慰剂对照,因此不能对其在 EVD 中的疗效得出任何结论。相比之下,来自安慰剂对照试验的数据显示对 COVID-19 患者有益。瑞德西韦缩短了需要补充氧气的住院患者康复的时间,可能对死亡率结果产生积极影响,同时具有良好的安全性。尽管这是对抗 COVID-19 的一个重要里程碑,但批准该药物不足以解决当前大流行所带来的公共卫生问题。还需要进一步的科学努力来评估核苷类似物作为治疗或预防病毒呼吸道感染的全部潜力,并开发出具有口服生物利用度的有效抗病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/222d/7566896/f2a90e4040db/CMR.00162-20-f0001.jpg

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