The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2

Xie, Yixin; Guo, Wenhan; Lopez-Hernadez, Alan; Teng, Shaolei; Li, Lin

COVID-19 has been threatening human health since the late 2019, which has significant impact n human health and economy. Understanding the SARS-CoV-2 and other coronaviruses is important to develop effective treatments for COVID-19 and other coronaviruses-caused diseases. In this work, we applied multi-scale computational approaches to study the electrostatic features of spike (S) proteins for SARS-CoV and SARS-CoV-2. From our results, we found that SARS-CoV and SARS-CoV-2 have similar charge distributions and electrostatic features when binding with the human angiotensin-converting enzyme 2 (hACE2). The energy pH-dependence calculations revealed that the complex structures of hACE2 and the S proteins of SARS-CoV/SARS-CoV-2 are stable at pH values ranging from 7.5 to 9. Molecular dynamics simulations were performed using NAMD to investigate the hydrogen bonds between S proteins and hACE2. From the MD simulations it was found that SARS-CoV-2 has four pairs of essential hydrogen bonds (high occupancy, >80%), while SARS-CoV has three pairs, which indicates the SARS-CoV-2 S protein has relatively more robust binding strategy than SARS-CoV S protein. Four key residues forming essential hydrogen bonds from SARS-CoV-2 are identified, which are potential drug targets for COVID-19 treatments. The findings in this study shed lights on the current and future treatments for COVID-19 and other coronaviruses-caused diseases.