Fig. 3: The antigenic drift paradigm of influenza viruses and coronaviruses.

a, Structural models of the HA protein of influenza A virus H1N1 from 1999 and 2006 isolates (PDBs 5C0S and 6CF7, respectively), in which mutated residues are highlighted in red and are shown on a single monomer of each trimer. Loss of neutralization titres against parental and drifted strains of H1N1, as previously described⁶⁵. b, Protein distance of major glycoproteins of influenza viruses. Dendrograms show the protein distance of HA amino acid sequences that are representative of the variability of each virus family. Shown are HAs from all 18 influenza A virus subtypes (multiple strains shown for H1, H3 and H5) and of HAs from influenza B virus from the ancestral virus from 1940 and the two Victoria and Yamagata lineages. Scale bar, 0.100. c, Timeline of influenza pandemics. d, e, The spike ectodomain of SARS-CoV-2 (d; PDB 6VYb; spike in the open conformation) and the spike ectodomain of HCoV-229E (e; PDB 6U7H), in which mutated residues are highlighted in red and are shown on a single monomer of each trimer. Loss of neutralization titres against parental and drifted strains of SARS-CoV-2 and HCoV-229E by serum antibodies elicited against the parental strains, as determined previously^1,82. f, Protein distance of spike glycoproteins of human and animal coronaviruses. Sarbecoviruses are shown according to the phylogenetic definition of RBD clades⁸³. Scale bar, 0.100. g, Timeline of the emergence of human coronaviruses. The emergence of common-cold coronaviruses is approximate and based on molecular clock dating⁸⁴. Highlighted in red in b and f are viral strains used in a, d and e.