> Mutation N501Y is one of six key contact residues within the receptor-binding domain (RBD) and has been identified as increasing binding affinity to human

> Mutation N501Y is one of six key contact residues within the receptor-binding domain (RBD) and has been identified as increasing binding affinity to human and murine ACE2. > The spike deletion 69-70del has been described in the context of evasion to the human immune response but has also occurred a number of times in association with other RBD changes. > Mutation P681H is immediately adjacent to the furin cleavage site, a known location of biological significance.... > nucleotide changes on this branch are predominantly amino acid-altering (14 non-synonymous mutations and 3 deletions). There are 6 synonymous mutations on the branch. This is suggestive of a process involving adaptive molecular evolution > These include spike position 501, one of the key contact residues in the receptor binding domain (RBD), and experimental data suggests mutation N501Y can increase ACE2 receptor affinity (Starr et al. 2020) and P681H, one of 4 residues comprising the insertion that creates a furin cleavage site between S1 and S2 in spike. The S1/S2 furin cleavage site of SARS-CoV-2 is not found in closely related coronaviruses and has been shown to promote entry into respiratory epithelial cells and transmission in animal models (Hoffmann, Kleine-Weber, and Pöhlmann 2020; Peacock et al. 2020; Zhu et al. 2020). N501Y has been associated with increased infectivity and virulence in a mouse model (Gu et al. 2020). Both N501Y and P681H have been observed independently but not to our knowledge in combination before now. > deletion of two amino acids at sites 69-70 in spike ... arose in the mink-associated outbreak in Denmark on the background of the Y453F RBD mutation This doesn't sound good