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Impact of temperature on the affinity of SARS-CoV-2 Spike glycoprotein for host ACE2.
Journal of Biological Chemistry ( IF 4.0 ) Pub Date : 2021-08-31 , DOI: 10.1016/j.jbc.2021.101151
Jérémie Prévost 1 , Jonathan Richard 1 , Romain Gasser 1 , Shilei Ding 2 , Clément Fage 3 , Sai Priya Anand 4 , Damien Adam 5 , Natasha Gupta Vergara 6 , Alexandra Tauzin 1 , Mehdi Benlarbi 2 , Shang Yu Gong 4 , Guillaume Goyette 2 , Anik Privé 2 , Sandrine Moreira 7 , Hugues Charest 7 , Michel Roger 8 , Walther Mothes 9 , Marzena Pazgier 10 , Emmanuelle Brochiero 5 , Guy Boivin 3 , Cameron F Abrams 6 , Arne Schön 11 , Andrés Finzi 12
Affiliation  

The seasonal nature of outbreaks of respiratory viral infections with increased transmission during low temperatures has been well established. Accordingly, temperature has been suggested to play a role on the viability and transmissibility of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The receptor-binding domain (RBD) of the Spike glycoprotein is known to bind to its host receptor angiotensin-converting enzyme 2 (ACE2) to initiate viral fusion. Using biochemical, biophysical, and functional assays to dissect the effect of temperature on the receptor-Spike interaction, we observed a significant and stepwise increase in RBD-ACE2 affinity at low temperatures, resulting in slower dissociation kinetics. This translated into enhanced interaction of the full Spike glycoprotein with the ACE2 receptor and higher viral attachment at low temperatures. Interestingly, the RBD N501Y mutation, present in emerging variants of concern (VOCs) that are fueling the pandemic worldwide (including the B.1.1.7 (α) lineage), bypassed this requirement. This data suggests that the acquisition of N501Y reflects an adaptation to warmer climates, a hypothesis that remains to be tested.

中文翻译:

温度对 SARS-CoV-2 Spike 糖蛋白与宿主 ACE2 亲和力的影响。

呼吸道病毒感染爆发的季节性特征以及低温期间传播的增加已得到充分证实。因此,有人认为温度对 SARS-CoV-2(导致 COVID-19 大流行的病毒)的生存力和传播性有影响。已知刺突糖蛋白的受体结合域 (RBD) 与其宿主受体血管紧张素转换酶 2 (ACE2) 结合以启动病毒融合。使用生物化学、生物物理和功能测定来剖析温度对受体-刺突相互作用的影响,我们观察到低温下 RBD-ACE2 亲和力显着且逐步增加,导致解离动力学减慢。这转化为完整 Spike 糖蛋白与 ACE2 受体的相互作用增强,以及低温下更高的病毒附着。有趣的是,RBD N501Y 突变存在于正在加剧全球大流行的新兴关注变体 (VOC) 中(包括 B.1.1.7 (α) 谱系),却绕过了这一要求。该数据表明,N501Y 的获得反映了对温暖气候的适应,这一假设仍有待检验。
更新日期:2021-08-31
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