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

J Biol Chem. 2021 Oct;297(4):101151. doi: 10.1016/j.jbc.2021.101151. Epub 2021 Aug 31.


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.

Keywords: ACE2; COVID-19; N501Y; RBD; SARS-CoV-2; Spike glycoproteins; coronavirus; neutralization; temperature; variants of concern.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Calorimetry
  • Humans
  • Interferometry
  • Polymorphism, Single Nucleotide
  • Protein Binding
  • Protein Structure, Quaternary
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Temperature
  • Thermodynamics


  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Angiotensin-Converting Enzyme 2