Fig. 2: Analysis of alterations in SARS2-N501YMA30 that arise during mouse adaptation.
From: Eicosanoid signalling blockade protects middle-aged mice from severe COVID-19
a, Schematic showing the genome of SARS-CoV-2. Initial N501Y alteration engineered into SARS-CoV-2 is shown in red. Viral proteins encoding alterations in SARS2-N501YMA30 are shaded in yellow and the corresponding alterations are highlighted in blue. ORF1a, open reading frame 1a. b, Summary of alterations that emerged in different virus passages. P30 virus is highlighted in green c, In silico modelling of the effects of alterations that emerged in serial mouse passaging on the affinity and stability of the S protein complexes with mACE2. d, Percentage of initial weight (left) and survival (right) of young BALB/c mice infected with viruses from two distinct plaque isolates purified from P30 virus. Virus from plaque 30.1 (black) encodes an extra alteration (E484K) in the S protein compared to virus from plaque 30.4 (blue) (n = 6 for both groups). e, Modelling of the receptor-binding interface between the S protein of 2019-nCoV/USA-WA1/2020 (left) and SARS2-N501YMA30 (right) viruses and mACE2 reveals critical interactions mediated by alterations that emerged through serial passaging. f, Percentage of initial weight (left) and survival (right) of young BALB/c mice and young or old C57BL/6 mice infected with 105 PFUs of B1.351 (n = 7 for young BALB/c; n = 8 for young C57BL/6; n = 9 for middle-aged C57BL/6). Data in d and f (left) are mean ± s.e.m.
