Revealing the Mechanism of SARS-CoV-2 Spike Protein Binding With ACE2

A large population in the world has been infected by COVID-19. Understanding the mechanisms of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is important for the management and treatment of COVID-19. When it comes to the infection process, one of the most important proteins in SARS-CoV-2 is the spike (S) protein, which is able to bind to human Angiotensin-Converting Enzyme 2 (ACE2) and initializes the entry of the host cell. In this study, we implemented multiscale computational approaches to study the electrostatic features of the interfaces of the SARS-CoV-2 S protein receptor binding domain and ACE2. The simulations and analyses were performed on high-performance computing resources in the Texas Advanced Computing Center. Our study identified key residues on SARS-CoV-2, which can be used as targets for future drug design. The results shed light on future drug design and therapeutic targets for COVID-19.

[1]  Emil Alexov,et al.  Multiscale method for modeling binding phenomena involving large objects: application to kinesin motor domains motion along microtubules , 2016, Scientific Reports.

[2]  Dominic M. Dousa.  THE UNIVERSITY OF TEXAS AT EL PASO , 2004 .

[3]  C. Karki,et al.  The Roles of Electrostatic Interactions in Capsid Assembly Mechanisms of Giant Viruses , 2019, International journal of molecular sciences.

[4]  Lin Li,et al.  DelPhi: a comprehensive suite for DelPhi software and associated resources , 2012, BMC biophysics.

[5]  Chuan Li,et al.  Highly efficient and exact method for parallelization of grid‐based algorithms and its implementation in DelPhi , 2012, J. Comput. Chem..

[6]  K. Sharp,et al.  Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models , 1994 .

[7]  S. Perlman,et al.  Coronaviruses: An Overview of Their Replication and Pathogenesis , 2015, Methods in molecular biology.

[8]  Lin Li,et al.  On the energy components governing molecular recognition in the framework of continuum approaches , 2015, Front. Mol. Biosci..

[9]  Tiantian Han,et al.  Coronavirus infections and immune responses , 2020, Journal of medical virology.

[10]  Jiahua He,et al.  Molecular Mechanism of Evolution and Human Infection with SARS-CoV-2 , 2020, Viruses.

[11]  E. Holmes,et al.  A new coronavirus associated with human respiratory disease in China , 2020, Nature.

[12]  Emil Alexov,et al.  Cytoplasmic dynein binding, run length, and velocity are guided by long-range electrostatic interactions , 2016, Scientific Reports.