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The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi. org/10.1101 org/10. /2020 nCoV [6] . Therefore, it is reasonable to hypothesize that the new coronavirus uses the 1 similar binding interface with ACE2 as SARS to enter host cells of human. The obvious [20-26]. Therefore, here we developed a multiscale computational strategy to compare 10 the process of recognition between the SARS-CoV and host cells with the interactions 11 between the new coronavirus and host cells. A mesoscale model is used to simulate the 12 process in which the coronaviruses are captured by ACE2 receptors on cell surface. We 13 further constructed a structural model for complex formed between ACE2 and RBD of 14 2019-nCoV S-protein, so that the rate of their association can be estimated by a coarse-15 grained Monte-Carlo simulation and further compared with the binding of S-protein from 16 SARS-CoV. Our simulation indicates that association of the new virus to the receptor is 17 slower than SARS, which is consistent with the experimental data obtained very recently. 18 We integrated this difference of association rate between virus and receptor into a simple 19 mathematical model which describes the life cycle of virus in host cells and its interplay 20 with the innate immune system. Interestingly, we found that the slower association 21 between virus and receptor can result in longer incubation period, while still maintaining 22 a relatively higher level of viral concentration in human body. Our computational study 23 therefore explains, from the molecular level, why the new COVID-19 disease is by far 24 more contagious than SARS. In summary, this multiscale model serves as a useful 25 addition to current understanding for the spread of coronaviruses and related infectious 26 agents.