A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells

Zhaoqian Su; Yinghao Wu

The coronavirus disease 2019 has emerged at the end of year 2019 2 from Wuhan, a city in China, as a new infectious disease [1, 2] . It has been found that the replicated RNA genome and synthesized viral proteins are finally assembled together into 10 new viruses, before they escape and attack other cells [7, 8] . As a result, the infections of 11 2019-nCoV normally come with the similar symptoms as SARS, including fever, 12 respiratory difficulty and pneumonia [9, 10] . Different from SARS, however, the new 13 COVID-19 seems to have longer incubation period and thus is more contagious [11] . The 14 disease has caused more than 70,000 confirmed cases with at least 1000 death globally, 15 according to the data from the World Health Organization (WHO) on February 16 th 2020. 16 Therefore, the development of vaccine or therapeutic treatment for this ongoing public 17 health crisis is highly demanding [12, 13] . 18 Almost all the coronaviruses recognize their host cells through spike (S) proteins 19 [14, 15] . S-protein is a glycoprotein expressed on the surface of viral envelop as homo-20 trimers [16] . Each S-protein further consists of two subunits. The S1 subunit includes a 21 region called receptor-binding domain (RBD) which is used to target receptors in host 22 cells, while the S2 subunit regulates the membrane fusion between virus and host cells 23 [17] . These roles of S protein suggest that it could be a key target for vaccine and 24 therapeutics developed to neutralize virus infection by blocking their invasion [18] . 25 Moreover, it has been confirmed in a recent report that the new virus 2019-nCoV uses the 26 same cell entry receptor ACE2 as SARS coronavirus [19] . The atomic structures of 27 complex between human ACE2 and the RBD regions from S-protein of SARS-CoV have 28 been obtained by x-ray crystallography [17] . It was also shown that the sequence of S-29 protein from SARS-CoV shares more than 70% identity with the S-protein from 2019-30 author/funder. All rights reserved. No reuse allowed without permission.