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2019冠状病毒病感染的抗病毒治疗:在持续的大流行中与时间赛跑。

Anti-viral treatment for SARS-CoV-2 infection: A race against time amidst the ongoing pandemic.

作者信息

Vallianou Natalia G, Tsilingiris Dimitrios, Christodoulatos Gerasimos Socrates, Karampela Irene, Dalamaga Maria

机构信息

First Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou str, 10676, Athens, Greece.

First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, 17 St Thomas street, 11527, Athens, Greece.

出版信息

Metabol Open. 2021 Jun;10:100096. doi: 10.1016/j.metop.2021.100096. Epub 2021 May 25.

Abstract

Remdesivir (GS-5734), a drug initially developed to treat hepatitis C and Ebola virus disease, was the first approved treatment for severe coronavirus disease 2019 (COVID-19). However, apart from remdesivir, there is a paucity of other specific anti-viral agents against SARS-CoV-2 infection. In 2017, researchers had documented the anti-coronavirus potential of remdesivir in animal models. At the same time, trials performed during two Ebola outbreaks in Africa showed that the drug was safe. Although vaccines against SARS-CoV-2 infection have emerged at an enormously high speed, equivalent results from efforts towards the development of anti-viral drugs, which could have played a truly life-saving role in the current stage of the pandemic, have been stagnating. In this review, we will focus on the current treatment options for COVID-19 which mainly consist of repurposed agents or treatments conferring passive immunity (convalescent plasma or monoclonal antibodies). Additionally, potential specific anti-viral therapies under development will be reviewed, such as the decoy miniprotein CTC-445.2d, protease inhibitors, mainly against the Main protein Mpro, nucleoside analogs, such as molnupiravir and compounds blocking the replication transcription complex proteins, such as zotatifin and plitidepsin. These anti-viral agents seem to be very promising but still require meticulous clinical trial testing in order to establish their efficacy and safety. The continuous emergence of viral variants may pose a real challenge to the scientific community towards that end. In this context, the advent of nanobodies together with the potential administration of a combination of anti-viral drugs could serve as useful tools in the armamentarium against COVID-19.

摘要

瑞德西韦(GS-5734)是一种最初开发用于治疗丙型肝炎和埃博拉病毒病的药物,是首个被批准用于治疗重症2019冠状病毒病(COVID-19)的药物。然而,除了瑞德西韦之外,针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的其他特异性抗病毒药物却很少。2017年,研究人员在动物模型中记录了瑞德西韦的抗冠状病毒潜力。与此同时,在非洲两次埃博拉疫情期间进行的试验表明,该药物是安全的。尽管针对SARS-CoV-2感染的疫苗已以极快的速度问世,但在大流行现阶段本可发挥真正救命作用的抗病毒药物研发工作所取得的相应成果却一直停滞不前。在这篇综述中,我们将重点关注COVID-19的当前治疗选择,这些选择主要包括重新利用的药物或赋予被动免疫的治疗方法(康复期血浆或单克隆抗体)。此外,还将综述正在研发的潜在特异性抗病毒疗法,例如诱饵小蛋白CTC-445.2d、主要针对主要蛋白酶Mpro的蛋白酶抑制剂、核苷类似物(如莫努匹韦)以及阻断复制转录复合体蛋白的化合物(如佐他芬和普利替辛)。这些抗病毒药物似乎很有前景,但仍需要进行细致的临床试验测试,以确定其疗效和安全性。病毒变体的不断出现可能会给科学界在这方面带来真正的挑战。在这种背景下,纳米抗体的出现以及抗病毒药物联合使用的可能性可成为抗击COVID-19的有用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb8f/8176363/1e4fa653b00c/gr1.jpg

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