Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein.
Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein.
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DOI：
10.1038/s41541-020-00246-8
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发表时间：
2020
期刊：
影响因子：
9.2
通讯作者：
Vasan SS
中科院分区：
文献类型：
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作者：
McAuley AJ;Kuiper MJ;Durr PA;Bruce MP;Barr J;Todd S;Au GG;Blasdell K;Tachedjian M;Lowther S;Marsh GA;Edwards S;Poole T;Layton R;Riddell SJ;Drew TW;Druce JD;Smith TRF;Broderick KE;Vasan SS
据推测，SARS-CoV-2刺突蛋白的“D 614 G”突变（第614位天冬氨酸变为甘氨酸）对大多数针对该糖蛋白的疫苗和对策的效力产生不利影响，因此需要频繁的疫苗匹配。使用接种了两剂INO-4800 COVID-19疫苗的雪貂血清和澳大利亚病毒分离株（VIC 01、SA 01和VIC 31）进行病毒中和试验，这些病毒分离株具有或缺乏该突变，但在其他方面具有可比性。通过这种方法，由这种突变的生物分子建模和RNA依赖性RNA聚合酶中通常相关的P314 L突变的支持，我们已经表明，没有实验证据支持这种推测。我们还证明，推定的弹性蛋白酶切割位点引入的D 614 G突变是不太可能接近蛋白酶。
The ‘D614G’ mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation. We additionally demonstrate that the putative elastase cleavage site introduced by the D614G mutation is unlikely to be accessible to proteases.