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展望 COVID-19 的潜在蛋白质靶点作为可成药部位。

An outlook on potential protein targets of COVID-19 as a druggable site.

机构信息

Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India.

出版信息

Mol Biol Rep. 2022 Nov;49(11):10729-10748. doi: 10.1007/s11033-022-07724-3. Epub 2022 Jul 6.

Abstract

BACKGROUND

SARS-CoV-2 which causes COVID-19 disease has started a pandemic episode all over the world infecting millions of people and has created medical and economic crisis. From December 2019, cases originated from Wuhan city and started spreading at an alarming rate and has claimed millions of lives till now. Scientific studies suggested that this virus showed genomic similarity of about 90% with SARS-CoV and is found to be more contagious as compared to SARS-CoV and MERS-CoV. Since the pandemic, virus has undergone constant mutation and few strains have raised public concern like Delta and Omicron variants of SARS-CoV-2.

OBJECTIVE

This review focuses on the structural features of SARS-CoV-2 proteins and host proteins as well as their mechanism of action. We have also elucidated the repurposed drugs that have shown potency to inhibit these protein targets in combating COVID-19. Moreover, the article discusses the vaccines approved so far and those under clinical trials for their efficacy against COVID-19.

CONCLUSION

Using cryo-electron microscopy or X-ray diffraction, hundreds of crystallographic data of SARS-CoV-2 proteins have been published including structural and non-structural proteins. These proteins have a significant role at different aspects in the viral machinery and presented themselves as potential target for drug designing and therapeutic interventions. Also, there are few host cell proteins which helps in SARS-CoV-2 entry and proteolytic cleavage required for viral infection.

摘要

背景

导致 COVID-19 疾病的 SARS-CoV-2 在全球范围内引发了大流行,感染了数百万人,并造成了医疗和经济危机。自 2019 年 12 月以来,源自武汉市的病例开始以惊人的速度传播,并导致至今已有数百万人死亡。科学研究表明,这种病毒与 SARS-CoV 的基因组相似度约为 90%,并且比 SARS-CoV 和 MERS-CoV 更具传染性。自大流行以来,病毒不断发生突变,少数毒株引起了公众关注,如 SARS-CoV-2 的 Delta 和奥密克戎变体。

目的

本综述重点介绍了 SARS-CoV-2 蛋白和宿主蛋白的结构特征及其作用机制。我们还阐明了已被重新利用的药物,这些药物在抑制这些蛋白靶点以对抗 COVID-19 方面显示出了效力。此外,本文还讨论了迄今为止已获得批准和正在临床试验中的疫苗,以评估它们对 COVID-19 的疗效。

结论

使用低温电子显微镜或 X 射线衍射,已经公布了数百个 SARS-CoV-2 蛋白的晶体学数据,包括结构蛋白和非结构蛋白。这些蛋白在病毒机制的不同方面发挥着重要作用,并成为药物设计和治疗干预的潜在靶点。此外,还有一些宿主细胞蛋白有助于 SARS-CoV-2 的进入和病毒感染所需的蛋白水解切割。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/950f/9256362/ad3e86341cc7/11033_2022_7724_Fig1_HTML.jpg

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