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SARS-CoV-2 非结构蛋白的遗传保守性 - 探索未来病毒爆发治疗的可能靶点。

Genetic conservation across SARS-CoV-2 non-structural proteins - Insights into possible targets for treatment of future viral outbreaks.

机构信息

Molecular Design Group, School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Pearse Street, Dublin, 2, Ireland.

Molecular Design Group, School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Pearse Street, Dublin, 2, Ireland.

出版信息

Virology. 2023 Apr;581:97-115. doi: 10.1016/j.virol.2023.02.011. Epub 2023 Mar 10.

Abstract

The majority of SARS-CoV-2 therapeutic development work has focussed on targeting the spike protein, viral polymerase and proteases. As the pandemic progressed, many studies reported that these proteins are prone to high levels of mutation and can become drug resistant. Thus, it is necessary to not only target other viral proteins such as the non-structural proteins (NSPs) but to also target the most conserved residues of these proteins. In order to understand the level of conservation among these viruses, in this review, we have focussed on the conservation across RNA viruses, conservation across the coronaviruses and then narrowed our focus to conservation of NSPs across coronaviruses. We have also discussed the various treatment options for SARS-CoV-2 infection. A synergistic melding of bioinformatics, computer-aided drug-design and in vitro/vivo studies can feed into better understanding of the virus and therefore help in the development of small molecule inhibitors against the viral proteins.

摘要

大多数针对 SARS-CoV-2 的治疗方法都集中在针对刺突蛋白、病毒聚合酶和蛋白酶上。随着大流行的发展,许多研究报告称这些蛋白质容易发生高水平突变并可能产生耐药性。因此,不仅需要针对其他病毒蛋白(如非结构蛋白 (NSP)),还需要针对这些蛋白的最保守残基。为了了解这些病毒之间的保守程度,在本综述中,我们专注于 RNA 病毒之间的保守性、冠状病毒之间的保守性,然后将重点缩小到冠状病毒中 NSP 的保守性。我们还讨论了针对 SARS-CoV-2 感染的各种治疗选择。生物信息学、计算机辅助药物设计和体外/体内研究的协同融合可以更好地了解病毒,从而有助于开发针对病毒蛋白的小分子抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd3f/9999249/6ddd8f40836a/ga1_lrg.jpg

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