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. 2020 Aug 1;26(9):663–669. doi: 10.1007/s11655-020-3427-6

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy

Tian-zi Wei 1,2,3, Hao Wang 4,5, Xue-qing Wu 4,5, Yi Lu 2, Sheng-hui Guan 1, Feng-quan Dong 5,6, Chen-le Dong 7, Gu-li Zhu 4,5, Yu-zhou Bao 5,6, Jian Zhang 2,✉, Guan-yu Wang 1,8,9,✉, Hai-ying Li 5,6,✉
PMCID: PMC7395204  PMID: 32740825

Abstract

Objective

To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening.

Methods

The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper.

Results

It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (莲花清瘟), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score.

Conclusions

A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.

Keywords: COVID-19, SARS-CoV-2, drug repurposing, virtual screening, Chinese medicine

Acknowledgment

Great thanks to Dr. JIANG Kai from Department of Biology, Southern University of Science and Technology for his suggestion on our experimental design and manuscript preparation.

Author Contributions

Li HY, Wang GY and Zhang J conceived and designed the study. Wei TZ and Wang H performed the research, and contributed to this work equally as co-first authors. All the authors analyzed the data. Li HY, Wang GY, Zhang J, WEI TZ, and Wang H wrote the manuscript draft. All the authors read and approved the final version of manuscript.

Footnotes

Supported by National Natural Science Foundation of China (No. 61773196), Special Scientific Research Project on COVID-19 Epidemic Prevention and Control in Guangdong Universities (No. 2020KZDZX1182), Guangdong Provincial Key Laboratory Funds (Nos. 2017B030301018, 2019B030301001), Shenzhen Research Funds (No. JCYJ20170817104740861), Shenzhen Peacock Plan (No. KQTD2016053117035204), and by Center for Computational Science and Engineering of Southern University of Science and Technology, China

Conflicts of Interest

The authors declare no conflict of interest.

Contributor Information

Jian Zhang, Email: zhangjian@sustech.edu.cn.

Guan-yu Wang, Email: wanggy@sustech.edu.cn.

Hai-ying Li, Email: lihaiying111@hotmail.com.

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