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用于病毒性疾病治疗药物开发的蛋白质折叠阻断策略:埃博拉病毒VP40和甲型流感病毒M1

Protein Folding Interdiction Strategy for Therapeutic Drug Development in Viral Diseases: Ebola VP40 and Influenza A M1.

作者信息

Bergasa-Caceres Fernando, Rabitz Herschel A

机构信息

Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.

出版信息

Int J Mol Sci. 2022 Mar 31;23(7):3906. doi: 10.3390/ijms23073906.

Abstract

In a recent paper, we proposed the folding interdiction target region (FITR) strategy for therapeutic drug design in SARS-CoV-2. This paper expands the application of the FITR strategy by proposing therapeutic drug design approaches against Ebola virus disease and influenza A. We predict target regions for folding interdicting drugs on correspondingly relevant structural proteins of both pathogenic viruses: VP40 of Ebola, and matrix protein M1 of influenza A. Identification of the protein targets employs the sequential collapse model (SCM) for protein folding. It is explained that the model predicts natural peptide candidates in each case from which to start the search for therapeutic drugs. The paper also discusses how these predictions could be tested, as well as some challenges likely to be found when designing effective therapeutic drugs from the proposed peptide candidates. The FITR strategy opens a potential new avenue for the design of therapeutic drugs that promises to be effective against infectious diseases.

摘要

在最近的一篇论文中,我们提出了用于严重急性呼吸综合征冠状病毒2(SARS-CoV-2)治疗药物设计的折叠阻断靶区(FITR)策略。本文通过提出针对埃博拉病毒病和甲型流感的治疗药物设计方法,扩展了FITR策略的应用。我们预测了针对这两种致病病毒相应相关结构蛋白的折叠阻断药物的靶区:埃博拉病毒的VP40和甲型流感的基质蛋白M1。蛋白质靶标的鉴定采用蛋白质折叠的顺序折叠模型(SCM)。文中解释说,该模型在每种情况下都能预测天然肽候选物,从而开始寻找治疗药物。本文还讨论了如何测试这些预测结果,以及从所提出的肽候选物设计有效治疗药物时可能会遇到的一些挑战。FITR策略为治疗药物的设计开辟了一条潜在的新途径,有望对传染病有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72cb/8998936/2c368c8997d8/ijms-23-03906-g001.jpg

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