PDF(Pubmed)
Abstract：
Since its first report in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a grave threat to public health. Virus-specific countermeasures, such as vaccines and therapeutics, have been developed and have contributed to the control of the viral pandemic, which has become endemic. Nonetheless, new variants continue to emerge and could cause a new pandemic. Consequently, it is important to comprehensively understand viral evolution and the roles of mutations in viral infectivity and transmission. SARS-CoV-2 beta variant encode mutations (D614G, N501Y, E484K, and K417N) in the spike which are frequently found in other variants as well. While their individual role in viral infectivity has been elucidated against various therapeutic antibodies, it still remains unclear whether those mutations may act additively or synergistically when combined. Here, we report that N501Y mutation shows differential effect on two therapeutic antibodies tested. Interestingly, the relative importance of E484K and K417N mutations in antibody evasion varies depending on the antibody type. Collectively, these findings suggest that continuous efforts to develop effective antibody therapeutics and combinatorial treatment with multiple antibodies are more rational and effective forms of treatment.
摘要：
自2019年首次报告以来，严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）对公众健康构成了严重威胁。病毒特异性对策，比如疫苗和治疗，已经开发并为控制病毒大流行做出了贡献，这已经成为地方病。尽管如此，新的变种继续出现，并可能导致新的大流行。因此,全面了解病毒进化和突变在病毒感染性和传播中的作用是重要的。SARS-CoV-2β变体编码突变(D614G，N501Y,E484K,和K417N）在其他变体中也经常发现的尖峰中。虽然它们在病毒感染性中的个体作用已经针对各种治疗性抗体进行了阐明，目前尚不清楚这些突变在联合使用时是否具有相加或协同作用.这里,我们报道,N501Y突变对所测试的两种治疗性抗体具有不同的作用.有趣的是,E484K和K417N突变在抗体逃避中的相对重要性因抗体类型而异.总的来说，这些发现表明，不断努力开发有效的抗体疗法和多抗体联合治疗是更合理和有效的治疗形式。
