Volume 42 Issue 2
Mar.  2021
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Chuan-Jun Shu, Xuan Huang, Hui-Hao Tang, Ding-Ding Mo, Jian-Wei Zhou, Cheng Deng. Mutations in spike protein and allele variations in ACE2 impact targeted therapy strategies against SARS-CoV-2. Zoological Research, 2021, 42(2): 170-181. doi: 10.24272/j.issn.2095-8137.2020.301
Citation: Chuan-Jun Shu, Xuan Huang, Hui-Hao Tang, Ding-Ding Mo, Jian-Wei Zhou, Cheng Deng. Mutations in spike protein and allele variations in ACE2 impact targeted therapy strategies against SARS-CoV-2. Zoological Research, 2021, 42(2): 170-181. doi: 10.24272/j.issn.2095-8137.2020.301

Mutations in spike protein and allele variations in ACE2 impact targeted therapy strategies against SARS-CoV-2

doi: 10.24272/j.issn.2095-8137.2020.301
#Authors contributed equally to this work
Funds:  This work was supported by the National Key Research and Development Program of China (2018YFD0900602), National Natural Science Foundation of China (31970388, 31701234), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Natural Science Foundation of the Jiangsu Higher Education Institutions (17KJB180006), Natural Science Foundation from Jiangsu Province (BK20160043, BK20151546, 15KJA180004 and BK20171035), and Jiangsu Distinguished Professor Funding
More Information
  • Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, however, no effective treatments or enough vaccines for COVID-19 are available. The roles of angiotensin converting enzyme 2 (ACE2) and spike protein in the treatment of COVID-19 are major areas of research. In this study, we explored the potential of ACE2 and spike protein as targets for the development of antiviral agents against SARS-CoV-2. We analyzed clinical data, genetic data, and receptor binding capability. Clinical data revealed that COVID-19 patients with comorbidities related to an abnormal renin-angiotensin system exhibited more early symptoms and poorer prognoses. However, the relationship between ACE2 expression and COVID-19 progression is still not clear. Furthermore, if ACE2 is not a good targetable protein, it would not be applicable across a wide range of populations. The spike-S1 receptor-binding domain that interacts with ACE2 showed various amino acid mutations based on sequence analysis. We identified two spike-S1 point mutations (V354F and V470A) by receptor-ligand docking and binding enzyme-linked immunosorbent assays. These variants enhanced the binding of the spike protein to ACE2 receptors and were potentially associated with increased infectivity. Importantly, the number of patients infected with the V354F and V470A mutants has increased with the development of the SARS-CoV-2 pandemic. These results suggest that ACE2 and spike-S1 are likely not ideal targets for the design of peptide drugs to treat COVID-19 in different populations.
  • #Authors contributed equally to this work
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