Mechanisms of SARS-CoV-2 Evolution Revealing Vaccine-Resistant Mutations in Europe and America
Mechanisms of SARS-CoV-2 Evolution Revealing Vaccine-Resistant Mutations in Europe and America
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DOI：
10.1021/acs.jpclett.1c03380
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发表时间：
2021-12-07
影响因子：
5.7
通讯作者：
Wei, Guo-Wei
中科院分区：
文献类型：
--
作者：
Wang, Rui;Chen, Jiahui;Wei, Guo-Wei
理解SARS-CoV-2进化的重要性不容忽视。最近的研究证实，自然选择是SARS-CoV-2进化的主导机制，它有利于增强病毒感染性的突变。在这里，我们证明了疫苗突破或抗体抗性突变提供了一种新的病毒进化机制。具体而言，在刺突蛋白受体结合结构域中的疫苗抗性突变Y 449 S，发生在共突变Y 449 S和N501 Y中，与原始SARS-CoV-2相比，感染性降低，但可以破坏现有的中和病毒的抗体。通过追踪超过220万个SARS-CoV-2基因组中疫苗耐药突变的进化轨迹，我们揭示了疫苗耐药突变的发生和频率与欧洲和美国的疫苗接种率密切相关。我们预计，作为一个补充的传播途径，疫苗突破或抗体耐药突变，如Omicron中的那些，将成为SARS-CoV-2进化的主导机制，当世界上大多数人口接种疫苗或感染时。我们的研究揭示了SARS-CoV-2的进化和传播，并使下一代抗突变疫苗和抗体药物的设计成为可能。
The importance of understanding SARS-CoV-2 evolution cannot be overlooked. Recent studies confirm that natural selection is the dominating mechanism of SARS-CoV-2 evolution, which favors mutations that strengthen viral infectivity. Here, we demonstrate that vaccine-breakthrough or antibody-resistant mutations provide a new mechanism of viral evolution. Specifically, vaccine-resistant mutation Y449S in the spike (S) protein receptor-binding domain, which occurred in co-mutations Y449S and N501Y, has reduced infectivity compared to that of the original SARS-CoV-2 but can disrupt existing antibodies that neutralize the virus. By tracking the evolutionary trajectories of vaccine-resistant mutations in more than 2.2 million SARS-CoV-2 genomes, we reveal that the occurrence and frequency of vaccine-resistant mutations correlate strongly with the vaccination rates in Europe and America. We anticipate that as a complementary transmission pathway, vaccine-breakthrough or antibody-resistant mutations, like those in Omicron, will become a dominating mechanism of SARS-CoV-2 evolution when most of the world's population is either vaccinated or infected. Our study sheds light on SARS-CoV-2 evolution and transmission and enables the design of the next-generation mutation-proof vaccines and antibody drugs.