Potential inhibitors for targeting Mpro and Spike of SARS-CoV-2 based on sequence and structural pharmacology analysis

  • Chuanjun Shu Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, 211166, China
  • Xuan Huang Reproductive Medical Center, Jinling Hospital Affiliated to The Medical School of Nanjing University, Nanjing, 210002, China
  • Ting Huang Department of Pharmacy, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, 221000, China
  • Li Chen Reproductive Medical Center, Jinling Hospital Affiliated to The Medical School of Nanjing University, Nanjing, 210002, China
  • Bing Yao Reproductive Medical Center, Jinling Hospital Affiliated to The Medical School of Nanjing University, Nanjing, 210002, China
  • Jianwei Zhou Department of Molecular Cell Biology & Toxicology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
  • Cheng Deng Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China
Keywords: SARS-CoV-2, Mpro, Spike, Structural pharmacology analysis, New peptide inhibitor


The SARS-CoV-2 outbreak has spread rapidly and widely since December 2019, and the effective drugs are urgently needed. The two key proteins, Mpro and Spike, are attractive therapy targets for developing drugs against SARS-CoV-2 infection. In this study, we searched for the potential inhibitors targeting Mpro and Spike based on protein sequences and structural pharmacological analysis. We found that both Mpro and Spike of SARS-CoV-2 were homologous with bat SARS-like-CoV. SARS-CoV-2 Mpro showed high conservation (sequence similarities >99%), and the existing few point mutants in different patients from diverse cities suggested that SARS-CoV-2 probably underwent adaptive evolution when the virus infection transmitted from Wuhan patients to other non-Wuhan patients. Moreover, some inhibitors for SARS-CoV Mpro could probably inhibit the activity of SARS-CoV-2 Mpro, because they do not target conserved mutated sites of SARS-CoV-2 Mpro, such as SDJ, ACE-THR-VAL-ALC-HIS-H, B4Z inhibitor, Beclabuvir, Saquinavir, and Lopinavir. In contrast, Spike of SARS-CoV-2 had more mutations and some mutant sites were distributed in the interaction domain between Spike and ACE2. A new peptide FRKSNLKPFERDISTEIYQAGSTPC, based on interactions between Spike and ACE2, could be a potential drug to treat SARS-CoV-2 patients. In summary, our study provided potential new inhibitors for targeting Mpro and Spike in SARS-CoV-2 virus-infected patients based on sequence and structural pharmacology analysis.


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How to Cite
Shu, C., Huang, X., Huang, T., Chen, L., Yao, B., Zhou, J., & Deng, C. (2020). Potential inhibitors for targeting Mpro and Spike of SARS-CoV-2 based on sequence and structural pharmacology analysis. STEMedicine, 1(2), e41. https://doi.org/10.37175/stemedicine.v1i2.41
Research articles