Devaux Christian A, Pinault Lucile, Delerce Jérémy, Raoult Didier, Levasseur Anthony, Frutos Roger
Aix-Marseille Université, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France.
CNRS, Marseille, France.
Front Microbiol. 2021 Sep 20;12:675528. doi: 10.3389/fmicb.2021.675528. eCollection 2021.
The rapid spread of SARS-CoV-2 variants has quickly spanned doubts and the fear about their ability escape vaccine protection. Some of these variants initially identified in caged were also found in humans. The claim that these variants exhibited lower susceptibility to antibody neutralization led to the slaughter of 17 million minks in Denmark. SARS-CoV-2 prevalence tests led to the discovery of infected farmed minks worldwide. In this study, we revisit the issue of the circulation of SARS-CoV-2 variants in minks as a model of sarbecovirus interspecies evolution by: (1) comparing human and mink angiotensin I converting enzyme 2 (ACE2) and neuropilin 1 (NRP-1) receptors; (2) comparing SARS-CoV-2 sequences from humans and minks; (3) analyzing the impact of mutations on the 3D structure of the spike protein; and (4) predicting linear epitope targets for immune response. Mink-selected SARS-CoV-2 variants carrying the Y453F/D614G mutations display an increased affinity for human ACE2 and can escape neutralization by one monoclonal antibody. However, they are unlikely to lose most of the major epitopes predicted to be targets for neutralizing antibodies. We discuss the consequences of these results for the rational use of SARS-CoV-2 vaccines.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的迅速传播很快消除了人们对其逃避疫苗保护能力的怀疑和恐惧。最初在圈养水貂中发现的一些变体也在人类中被发现。这些变体对抗体中和表现出较低敏感性的说法导致丹麦屠宰了1700万只水貂。SARS-CoV-2流行率检测导致在全球范围内发现受感染的养殖水貂。在本研究中，我们通过以下方式重新审视SARS-CoV-2变体在水貂中的传播问题，将其作为Sarbecovirus种间进化的一个模型：（1）比较人类和水貂的血管紧张素I转换酶2（ACE2）和神经纤毛蛋白1（NRP-1）受体；（2）比较来自人类和水貂的SARS-CoV-2序列；（3）分析突变对刺突蛋白三维结构的影响；（4）预测免疫反应的线性表位靶点。携带Y453F/D614G突变的水貂选择的SARS-CoV-2变体对人类ACE2表现出更高的亲和力，并且能够逃避一种单克隆抗体的中和作用。然而，它们不太可能失去大多数预计作为中和抗体靶点的主要表位。我们讨论了这些结果对合理使用SARS-CoV-2疫苗的影响。
