Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
Centro de Oncologia Molecular, Hospital Sírio Libanes, São Paulo 01308-060, Brazil.
Viruses. 2022 Apr 16;14(4):827. doi: 10.3390/v14040827.
Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host's immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) the increase in Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with the increase in RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment in Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron.
新型严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的关注变种（VOC）不断威胁着全球公共卫生。由于没有截止日期，随着新变种的出现，这种大流行仍在持续，这些新变种威胁着诊断测试和疫苗的有效性。病毒刺突表面蛋白经常观察到新变种中的突变，可能会产生与当前病毒不同嗜性的新型病毒，这可能会改变疾病的严重程度和症状。越来越多的证据表明，突变正在被选择有利于更能逃避中和抗体作用的变种。在这种情况下，指导 SARS-CoV-2 进化的最重要因素是它与宿主免疫系统的相互作用。因此，由于当前的疫苗不能阻止病毒的传播，接种疫苗以外的措施，如使用口罩、手部卫生和保持环境通风仍然是延迟新变种出现的关键。重要的是，除了免疫系统在病毒进化中的参与外，我们还强调了几个化学参数，这些参数影响病毒和宿主细胞在入侵过程中的分子相互作用，也是使新型变种更具传染性的关键工具。在这篇综述中，我们剖析了 Spike 突变对生物参数的影响，如（1） Spike 与 hACE2 结合亲和力的增加；（2）受体被蛋白酶切割的结合时间；（3）突变如何与 Spike 外域中 RBD 构象状态的增加相关联；（4）未切割 Spike 蛋白在病毒粒子中的扩展；（5）每个病毒粒子中的 Spike 浓度增加；以及（6）逃避免疫系统。这些因素在 SARS-CoV-2 关注变种（包括奥密克戎）的快速传播中发挥着关键作用。
