Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets

Pei Chen Yu; Chen Hao Huang; Chih Jung Kuo; Po Huang Liang; Lily Hui Ching Wang; Max Yu Chen Pan; Sui Yuan Chang; Tai Ling Chao; Si Man Ieong; Jun Tung Fang; Hsuan Cheng Huang; Hsueh Fen Juan

doi:10.3390/pharmaceutics14010176

Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets

Pei Chen Yu, Chen Hao Huang, Chih Jung Kuo, Po Huang Liang, Lily Hui Ching Wang, Max Yu Chen Pan, Sui Yuan Chang, Tai Ling Chao, Si Man Ieong, Jun Tung Fang, Hsuan Cheng Huang^*, Hsueh Fen Juan^*

^*Corresponding author for this work

Institute of Biomedical Informatics

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PL^pro), and 3C-like protease (3CL^pro) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding domain (RBD) was considered an important factor in the present assessment. Finally, the antiviral potency of compounds was validated using a plaque reduction assay. Our funnel strategy revealed that tamoxifen possesses an anti-SARS-CoV-2 property owing to its inhibitory performance in multiple assays. The proposed time-saving and feasible strategy may accelerate drug screening for COVID-19 and other diseases.

Original language	English
Article number	176
Journal	Pharmaceutics
Volume	14
Issue number	1
DOIs	https://doi.org/10.3390/pharmaceutics14010176
State	Published - Jan 2022

Keywords

3C-like protease (3CL/M)
Docking simulation
Papain-like protease (PL)
Severe acute respiratory syndrome coronavirus 2
Tamoxifen
Transmembrane protease serine 2 (TMPRSS2)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/pharmaceutics14010176

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title = "Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets",

abstract = "Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PLpro), and 3C-like protease (3CLpro) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding domain (RBD) was considered an important factor in the present assessment. Finally, the antiviral potency of compounds was validated using a plaque reduction assay. Our funnel strategy revealed that tamoxifen possesses an anti-SARS-CoV-2 property owing to its inhibitory performance in multiple assays. The proposed time-saving and feasible strategy may accelerate drug screening for COVID-19 and other diseases.",

keywords = "3C-like protease (3CL/M), Docking simulation, Papain-like protease (PL), Severe acute respiratory syndrome coronavirus 2, Tamoxifen, Transmembrane protease serine 2 (TMPRSS2)",

author = "Yu, {Pei Chen} and Huang, {Chen Hao} and Kuo, {Chih Jung} and Liang, {Po Huang} and Wang, {Lily Hui Ching} and Pan, {Max Yu Chen} and Chang, {Sui Yuan} and Chao, {Tai Ling} and Ieong, {Si Man} and Fang, {Jun Tung} and Huang, {Hsuan Cheng} and Juan, {Hsueh Fen}",

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year = "2022",

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doi = "10.3390/pharmaceutics14010176",

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AU - Yu, Pei Chen

AU - Huang, Chen Hao

AU - Kuo, Chih Jung

AU - Liang, Po Huang

AU - Wang, Lily Hui Ching

AU - Pan, Max Yu Chen

AU - Chang, Sui Yuan

AU - Chao, Tai Ling

AU - Ieong, Si Man

AU - Fang, Jun Tung

AU - Huang, Hsuan Cheng

AU - Juan, Hsueh Fen

PY - 2022/1

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AB - Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PLpro), and 3C-like protease (3CLpro) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding domain (RBD) was considered an important factor in the present assessment. Finally, the antiviral potency of compounds was validated using a plaque reduction assay. Our funnel strategy revealed that tamoxifen possesses an anti-SARS-CoV-2 property owing to its inhibitory performance in multiple assays. The proposed time-saving and feasible strategy may accelerate drug screening for COVID-19 and other diseases.

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KW - Transmembrane protease serine 2 (TMPRSS2)

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Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets

Abstract

Keywords

UN SDGs

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