Impact of temperature on the affinity of SARS-CoV-2 Spike glycoprotein for host ACE2

Jérémie Prévost,Alexandra Tauzin,Clément Fage,Shang Yu Gong,Michel Roger,Sandrine Moreira,Hugues Charest,Guillaume Goyette,Natasha Gupta Vergara,Sai Priya Anand,Romain Gasser,Arne Schön,Jonathan Richard,Walther Mothes,Guy Boivin,Anik Privé,Mehdi Benlarbi,Shilei Ding,Andrés Finzi,Damien Adam,Cameron F Abrams,Emmanuelle Brochiero,M Pazgier

doi:10.1016/j.jbc.2021.101151

Abstract

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.

Highlights

The seasonal nature of outbreaks of respiratory viral infections with increased transmission during low temperatures has been well established
Since it was previously documented that temperature modulates the affinity of another viral envelope glycoprotein (HIV-1 Env) for its receptor [24]; we evaluate to what extent temperature affects the interaction of SARS-CoV-2 Spike with angiotensinconverting enzyme 2 (ACE2) and concomitantly, its effect on viral attachment
EDITORS’ PICK: Low temperature enhances Spike–ACE2 affinity published structural data [25], ACE2 interacts with 17 key residues on the receptor-binding domain (RBD) primarily located on the receptor-binding motif (RBM)

Summary

Introduction

The seasonal nature of outbreaks of respiratory viral infections with increased transmission during low temperatures has been well established. Recent studies have noticed an increase replication of SARS-CoV-2 in primary human airway epithelial cells at 33 C compared with 37 C [22], while higher temperatures (39–40 C) decreased overall viral replication [23].

Results

Conclusion