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人类对抗 SARS-CoV-2 药物治疗的努力:抗击大流行的主要策略。

Human endeavor for anti-SARS-CoV-2 pharmacotherapy: A major strategy to fight the pandemic.

机构信息

Axe Molecular Endocrinology and Nephrology, CHU Research Center and Laval University, Quebec City, Quebec, G1V 4G2, Canada.

Axe Molecular Endocrinology and Nephrology, CHU Research Center and Laval University, Quebec City, Quebec, G1V 4G2, Canada.

出版信息

Biomed Pharmacother. 2021 May;137:111232. doi: 10.1016/j.biopha.2021.111232. Epub 2021 Jan 13.

Abstract

The global spread of COVID-19 constitutes the most dangerous pandemic to emerge during the last one hundred years. About seventy-nine million infections and more than 1.7 million death have been reported to date, along with destruction of the global economy. With the uncertainty evolved by alarming level of genome mutations, coupled with likelihood of generating only a short lived immune response by the vaccine injections, the identification of antiviral drugs for direct therapy is the need of the hour. Strategies to inhibit virus infection and replication focus on targets such as the spike protein and non-structural proteins including the highly conserved RNA-dependent-RNA-polymerase, nucleotidyl-transferases, main protease and papain-like proteases. There is also an indirect option to target the host cell recognition systems such as angiotensin-converting enzyme 2 (ACE2), transmembrane protease, serine 2, host cell expressed CD147, and the host furin. A drug search strategy consensus in tandem with analysis of currently available information is extremely important for the rapid identification of anti-viral. An unprecedented display of cooperation among the scientific community regarding SARS-CoV-2 research has resulted in the accumulation of an enormous amount of literature that requires curation. Drug repurposing and drug combinations have drawn tremendous attention for rapid therapeutic application, while high throughput screening and virtual searches support de novo drug identification. Here, we examine how certain approved drugs targeting different viruses can play a role in combating this new virus and analyze how they demonstrate efficacy under clinical assessment. Suggestions on repurposing and de novo strategies are proposed to facilitate the fight against the COVID-19 pandemic.

摘要

新冠病毒疫情在全球范围内的传播是过去 100 年来最危险的大流行病。截至目前,已报告约 7900 万例感染病例和超过 170 万人死亡,全球经济遭到破坏。由于基因组突变水平令人震惊,加上疫苗注射产生的免疫反应可能持续时间较短,因此迫切需要确定用于直接治疗的抗病毒药物。抑制病毒感染和复制的策略侧重于针对刺突蛋白和非结构蛋白的靶点,包括高度保守的 RNA 依赖性 RNA 聚合酶、核苷酸转移酶、主蛋白酶和木瓜蛋白酶样蛋白酶。还可以选择针对宿主细胞识别系统的间接策略,如血管紧张素转化酶 2(ACE2)、跨膜蛋白酶、丝氨酸 2、宿主细胞表达的 CD147 和宿主弗林蛋白酶。与分析当前可用信息相结合的药物搜索策略共识对于快速识别抗病毒药物至关重要。科学界在针对 SARS-CoV-2 研究方面的前所未有的合作,导致积累了大量需要整理的文献。药物再利用和药物组合引起了人们对快速治疗应用的极大关注,而高通量筛选和虚拟搜索则支持新药物的识别。在这里,我们研究了针对不同病毒的某些已批准药物如何在对抗这种新病毒方面发挥作用,并分析了它们在临床评估下如何显示疗效。提出了重新利用和新策略的建议,以促进对抗 COVID-19 大流行的斗争。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea28/7834004/76c2205f5880/ga1_lrg.jpg

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