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利用噬菌体展示技术发现抗病毒药物。

Discovery of Antivirals Using Phage Display.

机构信息

Department of Translational Proteomics, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.

Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada.

出版信息

Viruses. 2021 Jun 10;13(6):1120. doi: 10.3390/v13061120.

DOI:10.3390/v13061120
PMID:34200959
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8230593/
Abstract

The latest coronavirus disease outbreak, COVID-19, has brought attention to viral infections which have posed serious health threats to humankind throughout history. The rapid global spread of COVID-19 is attributed to the increased human mobility of today's world, yet the threat of viral infections to global public health is expected to increase continuously in part due to increasing human-animal interface. Development of antiviral agents is crucial to combat both existing and novel viral infections. Recently, there is a growing interest in peptide/protein-based drug molecules. Antibodies are becoming especially predominant in the drug market. Indeed, in a remarkably short period, four antibody therapeutics were authorized for emergency use in COVID-19 treatment in the US, Russia, and India as of November 2020. Phage display has been one of the most widely used screening methods for peptide/antibody drug discovery. Several phage display-derived biologics are already in the market, and the expiration of intellectual property rights of phage-display antibody discovery platforms suggests an increment in antibody drugs in the near future. This review summarizes the most common phage display libraries used in antiviral discovery, highlights the approaches employed to enhance the antiviral potency of selected peptides/antibody fragments, and finally provides a discussion about the present status of the developed antivirals in clinic.

摘要

最新的冠状病毒病疫情,即 COVID-19,引起了人们对病毒感染的关注,这些感染在历史上一直对人类健康构成严重威胁。COVID-19 在全球的迅速传播归因于当今世界人类流动性的增加,但由于人类与动物的接触不断增加,预计病毒感染对全球公共卫生的威胁将继续增加。开发抗病毒药物对于应对现有和新型病毒感染至关重要。最近,人们对肽/蛋白类药物分子越来越感兴趣。抗体在药物市场中越来越占据主导地位。事实上,截至 2020 年 11 月,美国、俄罗斯和印度已经有四种抗体疗法被授权用于 COVID-19 的紧急治疗。噬菌体展示技术是肽/抗体药物发现中最广泛使用的筛选方法之一。已经有几种噬菌体展示衍生的生物制剂上市,噬菌体展示抗体发现平台的知识产权即将到期,这表明在不久的将来抗体药物将会增加。本文综述了用于抗病毒发现的最常见的噬菌体展示文库,重点介绍了用于提高所选肽/抗体片段抗病毒效力的方法,最后讨论了目前临床开发的抗病毒药物的现状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf1/8230593/007e996c9e5e/viruses-13-01120-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf1/8230593/007e996c9e5e/viruses-13-01120-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf1/8230593/007e996c9e5e/viruses-13-01120-g001.jpg

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