Novel reporter constructs to accelerate antiviral and therapeutic discovery for Enterovirus-A71

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2025-02-01 DOI:10.1016/j.antiviral.2025.106094

William Bakhache , Ann Shen , Walker Symonds-Orr , Megan Culler Freeman , Patrick T. Dolan

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引用次数: 0

Abstract

Enterovirus A71 (EV-A71) is an important human pathogen and ‘prototype pathogen’ for studies of other Enteroviruses of pandemic potential. Understanding the biology of EV-A71 would inform generalizable strategies for antiviral drug, vaccine, and monoclonal antibody development. Such studies are accelerated by robust reagents to evaluate efficacy. Here, we describe and evaluate a suite of synthetic reporter constructs to accelerate EV-A71 research and therapeutic discovery. These constructs include replicons and infectious clones carrying luminescent and fluorescent reporter proteins. Among the reporters we tested were shorter luminescent and de novo-designed synthetic fluorescent proteins, which enhance genetic stability, reduce reporter gene loss and improve the utility of these reporters. This toolbox provides free access to robust and flexible assays for EV-A71 infection and replication through public repositories, promoting and accelerating open scientific discovery for this understudied emerging pathogen.

查看原文本刊更多论文

加速肠道病毒-A71 抗病毒和治疗发现的新型报告构建体。

肠病毒A71 （EV-A71）是一种重要的人类病原体，也是研究其他具有大流行潜力的肠病毒的“原型病原体”。了解EV-A71的生物学特性将为抗病毒药物、疫苗和单克隆抗体的开发提供可推广的策略。这样的研究可以通过强大的试剂来评估疗效。在这里，我们描述和评估了一套合成报告结构，以加速EV-A71的研究和治疗发现。这些结构包括复制子和携带发光和荧光报告蛋白的传染性克隆。在我们测试的报告蛋白中，有较短的发光蛋白和新设计的合成荧光蛋白，它们增强了遗传稳定性，减少了报告基因的损失，提高了这些报告蛋白的效用。该工具箱通过公共存储库免费提供EV-A71感染和复制的可靠和灵活的检测方法，促进和加速对这一未充分研究的新兴病原体的公开科学发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.