A deep learning-based drug repurposing screening and validation for anti-SARS-CoV-2 compounds by targeting the cell entry mechanism

Yingjia Yao, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China; National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China; Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110819, China.
Yunhan Zhang, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China; National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China; Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110819, China.
Zexu Li, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China; National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China; Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110819, China.
Zhisong Chen, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China; National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China; Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110819, China.
Xiaofeng Wang, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China; National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China; Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110819, China.
Zihan Li, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China; National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China; Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110819, China.
Li Yu, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Xiaolong Cheng, Center for Genetic Medicine Research, Children's National Hospital, 111 Michigan Ave NW, Washington, DC, 20010, USA; Department of Genomics and Precision Medicine, George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA.
Wei Li, Center for Genetic Medicine Research, Children's National Hospital, 111 Michigan Ave NW, Washington, DC, 20010, USA; Department of Genomics and Precision Medicine, George Washington University, 111 Michigan Ave NW, Washington, DC, 20010, USA.
Wen-Jie Jiang, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Hua-Jun Wu, Peking University Cancer Hospital and Institute, Beijing, 100142, China; Center for Precision Medicine Multi-Omics Research, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, 100191, Beijing, China.
Zezhong Feng, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Jinfu Sun, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Teng Fei, Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China; National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China; Key Laboratory of Data Analytics and Optimization for Smart Industry, Northeastern University, Ministry of Education, Shenyang, 110819, China. Electronic address: feiteng@mail.neu.edu.cn.

Document Type

Journal Article

Publication Date

7-12-2023

Journal

Biochemical and biophysical research communications

Volume

675

DOI

10.1016/j.bbrc.2023.07.018

Keywords

COVID-19; Drug; SARS-CoV-2; Target

Abstract

The recent outbreak of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a severe threat to the global public health and economy, however, effective drugs to treat COVID-19 are still lacking. Here, we employ a deep learning-based drug repositioning strategy to systematically screen potential anti-SARS-CoV-2 drug candidates that target the cell entry mechanism of SARS-CoV-2 virus from 2635 FDA-approved drugs and 1062 active ingredients from Traditional Chinese Medicine herbs. In silico molecular docking analysis validates the interactions between the top compounds and host receptors or viral spike proteins. Using a SARS-CoV-2 pseudovirus system, we further identify several drug candidates including Fostamatinib, Linagliptin, Lysergol and Sophoridine that can effectively block the cell entry of SARS-CoV-2 variants into human lung cells even at a nanomolar scale. These efforts not only illuminate the feasibility of applying deep learning-based drug repositioning for antiviral agents by targeting a specified mechanism, but also provide a valuable resource of promising drug candidates or lead compounds to treat COVID-19.

Department

Genomics and Precision Medicine

Link to Full Text

Share

COinS