SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses.
SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses.
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DOI：
10.1016/j.bbagen.2023.130319
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发表时间：
2023-04
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影响因子：
--
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中科院分区：
文献类型：
--
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七个冠状病毒已感染了迄今为止的人类（HCOV）。 SARS-COV-2引起了当前的COVID-19，与众所周知的高死亡率和严重的社会经济后果。 MERS-COV和SARS-COV分别引起MERS和SARS的流行，患有严重的呼吸道症状和严重的死亡。但是，HCOV-229E，HCOV-NL63，HCOV-HKU1和HCOV-OC43在大多数情况下会引起呼吸道疾病，其症状较小。所有冠状病毒都使用RNA限制来逃避人类的免疫系统。两种病毒甲基转移酶NSP14和NSP16在RNA封盖中起关键作用，被认为是抗脊髓灰病毒疗法的有价值的目标。但是，对于大多数HCOV的NSP10-NSP16甲基转移酶活性的动力学知之甚少，筛选的可靠测定法。在这里，我们报告了来自六个HCOV的NSP10-NSP16复合物与先前表征的SARS-COV-2并行的NSP10-NSP16复合物的表达，纯化和动力学表征。在SS148和WZ16探测所有七个的活性位点，两人最近报道了双NSP14 / NSP10-NSP16抑制剂。总体而言，我们的研究表明，开发宽光谱双NSP14 / NSP10-NSP16抑制剂疗法的可行性。
Seven coronaviruses have infected humans (HCoVs) to-date. SARS-CoV-2 caused the current COVID-19 pandemic with the well-known high mortality and severe socioeconomic consequences. MERS-CoV and SARS-CoV caused epidemic of MERS and SARS, respectively, with severe respiratory symptoms and significant fatality. However, HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43 cause respiratory illnesses with less severe symptoms in most cases. All coronaviruses use RNA capping to evade the immune systems of humans. Two viral methyltransferases, nsp14 and nsp16, play key roles in RNA capping and are considered valuable targets for development of anti-coronavirus therapeutics. But little is known about the kinetics of nsp10-nsp16 methyltransferase activities of most HCoVs, and reliable assays for screening are not available. Here, we report the expression, purification, and kinetic characterization of nsp10-nsp16 complexes from six HCoVs in parallel with previously characterized SARS-CoV-2. Probing the active sites of all seven by SS148 and WZ16, the two recently reported dual nsp14 / nsp10-nsp16 inhibitors, revealed pan-inhibition. Overall, our study show feasibility of developing broad-spectrum dual nsp14 / nsp10-nsp16-inhibitor therapeutics.
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影响因子：
6.7
作者：
Decroly E;Debarnot C;Ferron F;Bouvet M;Coutard B;Imbert I;Gluais L;Papageorgiou N;Sharff A;Bricogne G;Ortiz-Lombardia M;Lescar J;Canard B
通讯作者：
Canard B
影响因子：
--
作者：
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通讯作者：
Drosten C
DOI：
10.1080/07391102.2021.1916597
发表时间：
2021-04-12
影响因子：
4.4
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通讯作者：
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影响因子：
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作者：
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Boura, Evzen
影响因子：
11.5
作者：
Lamb YN
通讯作者：
Lamb YN