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SARS-CoV-1 和 SARS-CoV-2 宿主细胞融合的原子分辨率结构和膜动力学机制研究

Mechanistic insights of host cell fusion of SARS-CoV-1 and SARS-CoV-2 from atomic resolution structure and membrane dynamics.

机构信息

School of Chemistry, Sambalpur University, Jyoti Vihar, Burla, Odisha 768 019, India; Centre of Excellence in Natural Products and Therapeutics, Sambalpur University, Jyoti Vihar, Burla, Odisha 768 019, India.

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.

出版信息

Biophys Chem. 2020 Oct;265:106438. doi: 10.1016/j.bpc.2020.106438. Epub 2020 Jul 22.

Abstract

The emerging and re-emerging viral diseases are continuous threats to the wellbeing of human life. Previous outbreaks of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS had evidenced potential threats of coronaviruses in human health. The recent pandemic due to SARS-CoV-2 is overwhelming and has been going beyond control. Vaccines and antiviral drugs are ungently required to mitigate the pandemic. Therefore, it is important to comprehend the mechanistic details of viral infection process. The fusion between host cell and virus being the first step of infection, understanding the fusion mechanism could provide crucial information to intervene the infection process. Interestingly, all enveloped viruses contain fusion protein on their envelope that acts as fusion machine. For coronaviruses, the spike or S glycoprotein mediates successful infection through receptor binding and cell fusion. The cell fusion process requires merging of virus and host cell membranes, and that is essentially performed by the S2 domain of the S glycoprotein. In this review, we have discussed cell fusion mechanism of SARS-CoV-1 from available atomic resolution structures and membrane binding of fusion peptides. We have further discussed about the cell fusion of SARS-CoV-2 in the context of present pandemic situation.

摘要

新兴和再现的病毒性疾病是人类生命健康的持续威胁。严重急性呼吸综合征(SARS)和中东呼吸综合征(MERS)的先前爆发已经证明了冠状病毒对人类健康的潜在威胁。最近由 SARS-CoV-2 引起的大流行是压倒性的,已经失控。疫苗和抗病毒药物急需用于减轻大流行。因此,了解病毒感染过程的机制细节非常重要。宿主细胞与病毒之间的融合是感染的第一步,了解融合机制可以为干预感染过程提供关键信息。有趣的是,所有包膜病毒在其包膜上都含有融合蛋白,作为融合机器。对于冠状病毒,刺突或 S 糖蛋白通过受体结合和细胞融合介导成功感染。细胞融合过程需要病毒和宿主细胞膜的融合,这主要是由 S 糖蛋白的 S2 结构域完成的。在这篇综述中,我们根据现有的原子分辨率结构讨论了 SARS-CoV-1 的细胞融合机制和融合肽的膜结合。我们还讨论了在当前大流行背景下 SARS-CoV-2 的细胞融合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2d7/7375304/2cf1cb81f182/ga1_lrg.jpg

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