A nano-luciferase expressing human coronavirus OC43 for countermeasure development.
A nano-luciferase expressing human coronavirus OC43 for countermeasure development.
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DOI：
10.1016/j.virusres.2023.199286
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发表时间：
2024-01-02
期刊：
影响因子：
5
通讯作者：
Catanzaro, Nicholas J.
中科院分区：
文献类型：
--
作者：
Diefenbacher, Meghan, V;Baric, Thomas J.;Martinez, David R.;Baric, Ralph S.;Sheahan, Timothy P.;Catanzaro, Nicholas J.
表达纳米荧光素酶的HCoV-0 C43报告病毒的回收。HCoV-0 C43的复制在表达IFITM 3的Huh7.5细胞中增强。FDA批准的抗病毒药物有效抑制HCoV-OC 43复制。HCoV-OC 43 nLuc可以作为快速评估抗病毒对策的有用工具。冠状病毒（CoV）家族的遗传多样性对药物发现和开发构成了重大挑战。传统的抗病毒药物通常针对特定病毒的特定病毒蛋白，这限制了它们的使用，特别是针对新出现的病毒。具有广谱活性的抗病毒药物通过靶向病毒蛋白中对复制至关重要的高度保守区域或催化结构域来克服这一限制。为了快速鉴定具有广泛抗病毒活性的小分子，需要用代表全家族遗传多样性的病毒进行测定。经工程改造以表达报告基因（即发光、荧光等）的病毒可以增加药物筛选的效率、灵敏度或精确度，超过经典的复制测量，如观察细胞病变效应或测量感染滴度。我们以前已经开发了多个其他地方病，大流行，流行病和地方病CoV的报告病毒系统。人冠状病毒OC 43（HCoV-OC 43）是一种引起呼吸道感染的人地方性冠状病毒，其发病机制与年龄相关。在这里，我们描述了一种新的重组HCoV-OC 43报告病毒的发展，表达纳米荧光素酶（HCoV-OC 43 nLuc），其潜在的应用筛选抗冠状病毒。
Recovery of a HCoV-OC43 reporter virus expressing nanoluciferase. Replication of HCoV-OC43 is enhanced in IFITM3 expressing Huh7.5 cells. FDA-approved antivirals effectively inhibit HCoV-OC43 replication. HCoV-OC43 nLuc can be a useful tool to rapidly evaluate antiviral countermeasures. The genetic diversity of the coronavirus (CoV) family poses a significant challenge for drug discovery and development. Traditional antiviral drugs often target specific viral proteins from specific viruses which limits their use, especially against novel emerging viruses. Antivirals with broad-spectrum activity overcome this limitation by targeting highly conserved regions or catalytic domains within viral proteins that are essential for replication. For rapid identification of small molecules with broad antiviral activity, assays with viruses representing family-wide genetic diversity are needed. Viruses engineered to express a reporter gene (i.e. luminescence, fluorescence, etc.) can increase the efficiency, sensitivity or precision of drug screening over classical measures of replication like observation of cytopathic effect or measurement of infectious titers. We have previously developed reporter virus systems for multiple other endemic, pandemic, epidemic and enzootic CoV. Human CoV OC43 (HCoV-OC43) is a human endemic CoV that causes respiratory infection with age-related exacerbations of pathogenesis. Here, we describe the development of a novel recombinant HCoV-OC43 reporter virus that expresses nano-luciferase (HCoV-OC43 nLuc), and its potential application for screening of antivirals against CoV.
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影响因子：
11.1
作者：
Li, Pengfei;Wang, Yining;Lamers, Mart M.;Lavrijsen, Marla;Iriondo, Cinta;de Vries, Annemarie C.;Rottier, Robbert J.;Peppelenbosch, Maikel P.;Haagmans, Bart L.;Pan, Qiuwei
通讯作者：
Pan, Qiuwei
影响因子：
4.8
作者：
Hirose R;Watanabe N;Bandou R;Yoshida T;Daidoji T;Naito Y;Itoh Y;Nakaya T
通讯作者：
Nakaya T
影响因子：
7.6
作者：
Brown, Ariane J.;Won, John J.;Sheahan, Timothy P.
通讯作者：
Sheahan, Timothy P.
影响因子：
16.6
作者：
Prelli Bozzo C;Nchioua R;Volcic M;Koepke L;Krüger J;Schütz D;Heller S;Stürzel CM;Kmiec D;Conzelmann C;Müller J;Zech F;Braun E;Groß R;Wettstein L;Weil T;Weiß J;Diofano F;Rodríguez Alfonso AA;Wiese S;Sauter D;Münch J;Goffinet C;Catanese A;Schön M;Boeckers TM;Stenger S;Sato K;Just S;Kleger A;Sparrer KMJ;Kirchhoff F
通讯作者：
Kirchhoff F
影响因子：
5.4
作者：
Yount, B;Curtis, KM;Baric, RS
通讯作者：
Baric, RS