Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA.
Int J Clin Pract. 2020 Aug;74(8):e13525. doi: 10.1111/ijcp.13525. Epub 2020 Jun 3.
The COVID-19 pandemic is caused by infection with the SARS-CoV-2 virus. The major mutation detected to date in the SARS-CoV-2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation.
Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilise a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.
These results imply that G614 is a more pathogenic strain of SARS-CoV-2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID-19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection.
COVID-19 大流行是由感染 SARS-CoV-2 病毒引起的。到目前为止，在 SARS-CoV-2 病毒包膜刺突蛋白中检测到的主要突变是一种经常在中国株中发现的天冬氨酸（D）到 614 位甘氨酸（G）的突变，该突变负责病毒与宿主的附着，也是宿主抗体的主要靶标。我们试图推断这种突变对健康的影响。
各国病例死亡率与携带 G614 的病毒比例密切相关。614 位的氨基酸位于病毒刺突的内部蛋白界面，该位置的 G 存在会使病毒刺突的特定构象不稳定，其中关键的宿主受体结合位点更容易接近。
这些结果表明，G614 是一种更具致病性的 SARS-CoV-2 毒株，这可能会影响疫苗设计。这种病毒形式的流行也应包括在预测特定地区 COVID-19 健康负担和死亡率随时间变化的流行病学模型中。医生应该意识到这种病毒的特征，以预测感染的临床过程。
