Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

TLDR

A new highly pathogenic coronavirus, SARS‑CoV‑2, emerged in Wuhan in December 2019 and rapidly spread worldwide, and its spike protein’s receptor‑binding domain binds ACE2 in a mode nearly identical to that of SARS‑CoV. The study aimed to elucidate the initial infection step by determining the crystal structure of the SARS‑CoV‑2 spike RBD bound to ACE2 at atomic resolution. The authors crystallized the SARS‑CoV‑2 spike RBD in complex with ACE2 and solved its structure. The structure revealed that key ACE2‑binding residues are highly conserved or similar to SARS‑CoV, suggesting convergent evolution, and analysis of two SARS‑CoV antibody epitopes indicated potential cross‑reactivity with SARS‑CoV‑2.

Abstract

A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.