Yun Chen,Yao Guo,Yihang Pan,Zhizhuang Joe Zhao
Biochemical and Biophysical Research Communications
Available online 17 February 2020
Copyright © 2020, Elsevier
Structure analysis of the receptor binding of 2019-nCoV
A mysterious pneumonia illness was first reported in late December 2019 in Wuhan, China, and has rapidly spread to a dozen of countries including the United States with thousands of infected individuals and hundreds of deaths within a month . Scientists in China have isolated the virus from patients and determined its genetic code. The pathogen responsible for this epidemic is a new coronavirus designated 2019-nCoV by the World Health Organization. 2019-nCoV belongs to the same family of viruses as the well-known severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), which have killed hundreds of people in the past 17 years.
Coronaviruses consist of a large diverse family of viruses. They can be classified into four genera: Alpha-, Beta-, Gamma-, and Delta coronavirus [2,3]. Representative alphacoronaviruses include human coronavirus NL63 (HCoV-NL63), while the betacoronaviruses include the best-known SARS-CoV and MERS-CoV. Based on nucleic acid sequence similarity, the newly identified 2019-nCoV is a betacoronavirus. The entry of all coronaviruses into host cells is mediated by spike glycoprotein that gives coronaviruses a crown-like appearance by forming spikes on their surface. The amino acid sequence of spike glycoprotein consists of a large ectodomain, a single-pass transmembrane anchor, and a short C-terminal intracellular tail . The ectodomain contains a receptor-binding unit S1 and a membrane-fusion unit S2. Electron microscopic imaging illustrated that spike glycoprotein forms a clove-shaped spike with three S1 heads and a trimeric S2 stalk. For a virus to enter a host cell, S1 binds to a specific cell surface receptor via its receptor-binding domain (RBD), and S2 fuses the host cell and viral membranes, enabling the entry of viral genomes into host cells. Specific RBD-receptor binding determines if a cell or animal can be infected and also serves as a target for therapeutic inventions to treat diseases caused by coronaviruses. Previous studies have identified angiotensin converting enzyme 2 (ACE2) as a functional receptor for SARS-CoV [4,5]. In this study, we analyzed the structure of spike glycoprotein RBD of 2019-nCoV and identified a unique feature that potentially allows a high affinity binding to ACE2 in human cells. We further discussed potential candidates for natural hosts of 2019-nCoV, routes of transmission, and strategies to inhibit virus entry for therapeutic applications.
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