JIB-04 Has Broad-Spectrum Antiviral Activity and Inhibits SARS-CoV-2 Replication and Coronavirus Pathogenesis.

JIB-04 Has Broad-Spectrum Antiviral Activity and Inhibits SARS-CoV-2 Replication and Coronavirus Pathogenesis.
复制标题

JIB-04 具有广谱抗病毒活性并抑制 SARS-CoV-2 复制和冠状病毒发病机制

DOI:
10.1128/mbio.03377-21
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发表时间:
2022-02-22
期刊:
影响因子:
6.4
通讯作者:
Ding S
Ding S
中科院分区:
生物学1区
文献类型:
--
作者:
Son J;Huang S;Zeng Q;Bricker TL;Case JB;Zhou J;Zang R;Liu Z;Chang X;Darling TL;Xu J;Harastani HH;Chen L;Gomez Castro MF;Zhao Y;Kohio HP;Hou G;Fan B;Niu B;Guo R;Rothlauf PW;Bailey AL;Wang X;Shi PY;Martinez ED;Brody SL;Whelan SPJ;Diamond MS;Boon ACM;Li B;Ding S

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致病性冠状病毒是对全球公共卫生的重大威胁。在这里,使用基于重组报告病毒的化合物筛选方法,我们发现了小分子抑制剂,可以有效地阻断严重急性呼吸综合征病毒2 (SARS-CoV-2)的复制。其中,JIB-04抑制SARS-CoV-2在Vero E6细胞中的复制,50%有效浓度为695 nM,特异性指数大于1000。JIB-04在体外对多种细胞类型(包括原代人支气管上皮细胞)具有抗病毒活性,可对抗多种DNA和RNA病毒,包括猪冠状病毒传染性胃肠炎病毒。在猪体内冠状病毒感染模型中,注射JIB-04可减少病毒感染和相关组织病理,从而改善猪的体重增加和存活率。这些结果突出了JIB-04作为抗病毒药物对抗SARS-CoV-2和其他病毒性病原体的潜在效用。
Pathogenic coronaviruses are a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified small-molecule inhibitors that potently block the replication of severe acute respiratory syndrome virus 2 (SARS-CoV-2). Among them, JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with a 50% effective concentration of 695 nM, with a specificity index of greater than 1,000. JIB-04 showed in vitro antiviral activity in multiple cell types, including primary human bronchial epithelial cells, against several DNA and RNA viruses, including porcine coronavirus transmissible gastroenteritis virus. In an in vivo porcine model of coronavirus infection, administration of JIB-04 reduced virus infection and associated tissue pathology, which resulted in improved weight gain and survival. These results highlight the potential utility of JIB-04 as an antiviral agent against SARS-CoV-2 and other viral pathogens.
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