a | Schematic diagram of the spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. The residue numbers of each region correspond to their positions in the S proteins of SARS-CoV and SARS-CoV-2. The dark blue blocks represent insertions in the S protein. The insertions at amino acids 675–691 of the SARS-CoV-2 S protein are shown in an enlargement at the bottom right and aligned with those of other coronaviruses in the same region. b | Alignment of the receptor-binding domain (RBD) in SARS-CoV-2, SARS-CoV BJ01, RaTG13, pangolin coronavirus reported from Guangdong, China (GD pangolin), pangolin coronavirus reported from Guangxi, China (GX pangolin) and bat SARS-related coronavirus (SARSr-CoV) WIV1. The receptor-binding motif (RBM) is shown in purple, and the five key residues that contact angiotensin-converting enzyme 2 (ACE2) directly are highlighted in green. c | Five critical residues in the RBD of SARS-CoV-2 and other viruses. d | Comparison of the structure of SARS-CoV-2 and SARS-CoV RBD complexed with human ACE2 (hACE2); SARS-CoV-2 RBM in purple, SARS-CoV RBM in yellow and hACE2 in green). Five critical residues that are involved in the RBM–ACE2 binding are shown. The Protein Data Bank codes are 2AJF for SARS-CoV RBD–hACE2 and 6VW1 for SARS-CoV-2 RBD–hACE2. The GenBank entries are AY278488 for SARS-CoV BJ01, MN996532 for the bat SARSr-CoV RaTG13, MT121216 and MT072864 for the GD pangolin and GX pangolin coronaviruses, respectively, and KF367457 for the bat SARSr-CoV WIV1. CP, cytoplasmic domain; FP, fusion peptide; HR1, heptad repeat 1; HR2, heptad repeat 2; NTD, N-terminal domain; SP, signal peptide; TM, transmembrane domain. Parts a and b adapted from ref.26, Springer Nature Limited.