Abstract
A novel SARS-like coronavirus (2019-nCoV) recently emerged from Wuhan, China and is quickly spreading in humans. A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infection, pathogenesis, and host range. 2019-nCoV and SARS-CoV recognize the same host receptor ACE2. Here we determined the crystal structure of 2019-nCoV receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex of human ACE2.Compared with SARS-CoV, an ACE2-binding ridge in 2019-nCoV RBD takes more compact conformations, causing structural changes at the RBD/ACE2 interface. Adaptive to these structural changes, several mutations in 2019-nCoV RBD enhance ACE2- binding affinity, contributing to the high infectivity of 2019-CoV. These mutations also reveal the molecular mechanisms of the animal-to-human transmission of 2019-nCoV. Alarmingly, a single N439R mutation in 2019-nCoV RBD further enhances its ACE2- binding affinity, indicating possible future evolution of 2019-nCoV in humans. This study sheds light on the epidemiology and evolution of 2019-nCoV, and provides guidance for intervention strategies targeting receptor recognition by 2019-nCoV.
Structural Basis for Receptor Recognition by the Human CD59-Responsive Cholesterol-Dependent Cytolysins