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CSF3 Is a Potential Drug Target for the Treatment of COVID-19

Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease that appeared at the end of 2019. As of July 2020, the cumulative number of infections and deaths have exceeded 15 million and 630,000, respectively. And new cases are increasing. There are still many difficulties surroun...

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Autores principales: Fang, Chao, Mei, Jie, Tian, Huixiang, Liou, Yu-Ligh, Rong, Dingchao, Zhang, Wei, Liao, Qianjin, Wu, Nayiyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862719/
https://www.ncbi.nlm.nih.gov/pubmed/33551833
http://dx.doi.org/10.3389/fphys.2020.605792
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author Fang, Chao
Mei, Jie
Tian, Huixiang
Liou, Yu-Ligh
Rong, Dingchao
Zhang, Wei
Liao, Qianjin
Wu, Nayiyuan
author_facet Fang, Chao
Mei, Jie
Tian, Huixiang
Liou, Yu-Ligh
Rong, Dingchao
Zhang, Wei
Liao, Qianjin
Wu, Nayiyuan
author_sort Fang, Chao
collection PubMed
description Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease that appeared at the end of 2019. As of July 2020, the cumulative number of infections and deaths have exceeded 15 million and 630,000, respectively. And new cases are increasing. There are still many difficulties surrounding research on the mechanism and development of therapeutic vaccines. It is urgent to explore the pathogenic mechanism of viruses to help prevent and treat COVID-19. In our study, we downloaded two datasets related to COVID-19 (GSE150819 and GSE147507). By analyzing the high-throughput expression matrix of uninfected human bronchial organoids and infected human bronchial organoids in the GSE150819, 456 differentially expressed genes (DEGs) were identified, which were mainly enriched in the cytokine–cytokine receptor interaction pathway and so on. We also constructed the protein–protein interaction (PPI) network of DEGs to identify the hub genes. Then we analyzed GSE147507, which contained lung adenocarcinoma cell lines (A549 and Calu3) and the primary bronchial epithelial cell line (NHBE), obtaining 799, 460, and 46 DEGs, respectively. The results showed that in human bronchial organoids, A549, Calu3, and NHBE samples infected with SARS-CoV-2, only one upregulated gene CSF3 was identified. Interestingly, CSF3 is one of the hub genes we previously screened in GSE150819, suggesting that CSF3 may be a potential drug target. Further, we screened potential drugs targeting CSF3 by MOE; the top 50 drugs were screened by flexible docking and rigid docking, with 37 intersections. Two antiviral drugs (Elbasvir and Ritonavir) were included; Elbasvir and Ritonavir formed van der Waals (VDW) interactions with surrounding residues to bind with CSF3, and Elbasvir and Ritonavir significantly inhibited CSF3 protein expression.
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spelling pubmed-78627192021-02-06 CSF3 Is a Potential Drug Target for the Treatment of COVID-19 Fang, Chao Mei, Jie Tian, Huixiang Liou, Yu-Ligh Rong, Dingchao Zhang, Wei Liao, Qianjin Wu, Nayiyuan Front Physiol Physiology Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease that appeared at the end of 2019. As of July 2020, the cumulative number of infections and deaths have exceeded 15 million and 630,000, respectively. And new cases are increasing. There are still many difficulties surrounding research on the mechanism and development of therapeutic vaccines. It is urgent to explore the pathogenic mechanism of viruses to help prevent and treat COVID-19. In our study, we downloaded two datasets related to COVID-19 (GSE150819 and GSE147507). By analyzing the high-throughput expression matrix of uninfected human bronchial organoids and infected human bronchial organoids in the GSE150819, 456 differentially expressed genes (DEGs) were identified, which were mainly enriched in the cytokine–cytokine receptor interaction pathway and so on. We also constructed the protein–protein interaction (PPI) network of DEGs to identify the hub genes. Then we analyzed GSE147507, which contained lung adenocarcinoma cell lines (A549 and Calu3) and the primary bronchial epithelial cell line (NHBE), obtaining 799, 460, and 46 DEGs, respectively. The results showed that in human bronchial organoids, A549, Calu3, and NHBE samples infected with SARS-CoV-2, only one upregulated gene CSF3 was identified. Interestingly, CSF3 is one of the hub genes we previously screened in GSE150819, suggesting that CSF3 may be a potential drug target. Further, we screened potential drugs targeting CSF3 by MOE; the top 50 drugs were screened by flexible docking and rigid docking, with 37 intersections. Two antiviral drugs (Elbasvir and Ritonavir) were included; Elbasvir and Ritonavir formed van der Waals (VDW) interactions with surrounding residues to bind with CSF3, and Elbasvir and Ritonavir significantly inhibited CSF3 protein expression. Frontiers Media S.A. 2021-01-22 /pmc/articles/PMC7862719/ /pubmed/33551833 http://dx.doi.org/10.3389/fphys.2020.605792 Text en Copyright © 2021 Fang, Mei, Tian, Liou, Rong, Zhang, Liao and Wu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Fang, Chao
Mei, Jie
Tian, Huixiang
Liou, Yu-Ligh
Rong, Dingchao
Zhang, Wei
Liao, Qianjin
Wu, Nayiyuan
CSF3 Is a Potential Drug Target for the Treatment of COVID-19
title CSF3 Is a Potential Drug Target for the Treatment of COVID-19
title_full CSF3 Is a Potential Drug Target for the Treatment of COVID-19
title_fullStr CSF3 Is a Potential Drug Target for the Treatment of COVID-19
title_full_unstemmed CSF3 Is a Potential Drug Target for the Treatment of COVID-19
title_short CSF3 Is a Potential Drug Target for the Treatment of COVID-19
title_sort csf3 is a potential drug target for the treatment of covid-19
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862719/
https://www.ncbi.nlm.nih.gov/pubmed/33551833
http://dx.doi.org/10.3389/fphys.2020.605792
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