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.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, coronavirus, neutralization, variants of concern, ACE2, angiotensin-converting enzyme 2, RBD, receptor-binding domain, RBD, N501Y, spike glycoproteins, temperature, VOI, variant of interest, mAb, monoclonal antibody, WT, wild-type, RBM, receptor-binding motif, AEC, airway epithelial cell, BLI, biolayer interferometry, ITC, isothermal titration calorimetry, VOC, variant of concern, 【초록키워드】 pandemic, spike, COVID-19 pandemic, ACE2 receptor, Transmission, virus, angiotensin-converting enzyme 2, B.1.1.7, outbreak, viability, VOCs, Lineage, glycoprotein, N501Y mutation, respiratory viral infection, Interaction, Hypothesis, biochemical, host receptor, domain, transmissibility of SARS-CoV-2, acquisition, RBD-ACE2, responsible, resulting, tested, functional, suggested, the RBD, increase in, translated, dissect, reflect, bypassed, the Spike, effect of temperature, 【제목키워드】 spike, Impact, glycoprotein, Host,