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新型冠状病毒的潜在药物靶点:从基因组学到治疗学。

Potential drug targets of SARS-CoV-2: From genomics to therapeutics.

机构信息

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.

出版信息

Int J Biol Macromol. 2021 Apr 30;177:1-9. doi: 10.1016/j.ijbiomac.2021.02.071. Epub 2021 Feb 9.

Abstract

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from China has become a global threat due to the continuous rise in cases of Coronavirus disease 2019 (COVID-19). The problem with COVID-19 therapeutics is due to complexity of the mechanism of the pathogenesis of this virus. In this review, an extensive analysis of genome architecture and mode of pathogenesis of SARS-CoV-2 with an emphasis on therapeutic approaches is performed. SARS-CoV-2 genome consists of a single, ~29.9 kb long RNA having significant sequence similarity to BAT-CoV, SARS-CoV and MERS-CoV genome. Two-third part of SARS-Cov-2 genome comprises of ORF (ORF1ab) resulting in the formation of 2 polyproteins, pp1a and pp1ab, later processed into 16 smaller non-structural proteins (NSPs). The four major structural proteins of SARS-CoV-2 are the spike surface glycoprotein (S), a small envelope (E), membrane (M), and nucleocapsid (N) proteins. S protein helps in receptor binding and membrane fusion and hence plays the most important role in the transmission of CoVs. Priming of S protein is done by serine 2 transmembrane protease and thus plays a key role in virus and host cell fusion. This review highlights the possible mechanism of action of SARS-CoV-2 to search for possible therapeutic options.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的出现是一个全球性的威胁,因为 2019 年冠状病毒病(COVID-19)的病例持续上升。COVID-19 治疗药物的问题是由于该病毒发病机制的复杂性。在这篇综述中,对 SARS-CoV-2 的基因组结构和发病机制进行了广泛的分析,并重点介绍了治疗方法。SARS-CoV-2 基因组由一条长约 29.9kb 的单链 RNA 组成,与 BAT-CoV、SARS-CoV 和 MERS-CoV 基因组具有显著的序列相似性。SARS-CoV-2 基因组的三分之二部分包含 ORF(ORF1ab),导致形成 2 种多蛋白,pp1a 和 pp1ab,然后进一步加工成 16 种较小的非结构蛋白(NSPs)。SARS-CoV-2 的四种主要结构蛋白是刺突表面糖蛋白(S)、小包膜(E)、膜(M)和核衣壳(N)蛋白。S 蛋白有助于受体结合和膜融合,因此在 CoV 的传播中起着最重要的作用。S 蛋白的启动是由丝氨酸 2 跨膜蛋白酶完成的,因此在病毒和宿主细胞融合中起着关键作用。这篇综述强调了 SARS-CoV-2 的可能作用机制,以寻找可能的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3848/7871800/017f1cd23982/gr1_lrg.jpg

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