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Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2

The new coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been reported and spread globally. There is an urgent need to take urgent measures to treat and prevent further infection of this virus. Here, we use virtual drug screening to est...

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Autores principales: Chen, Chih-Chieh, Zhuang, Zhi-Jie, Wu, Chia-Wei, Tan, Yi-Ling, Huang, Chen-Hsiu, Hsu, Chia-Yi, Tsai, Eing-Mei, Hsieh, Tsung-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221610/
https://www.ncbi.nlm.nih.gov/pubmed/35741053
http://dx.doi.org/10.3390/cells11121924
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author Chen, Chih-Chieh
Zhuang, Zhi-Jie
Wu, Chia-Wei
Tan, Yi-Ling
Huang, Chen-Hsiu
Hsu, Chia-Yi
Tsai, Eing-Mei
Hsieh, Tsung-Hua
author_facet Chen, Chih-Chieh
Zhuang, Zhi-Jie
Wu, Chia-Wei
Tan, Yi-Ling
Huang, Chen-Hsiu
Hsu, Chia-Yi
Tsai, Eing-Mei
Hsieh, Tsung-Hua
author_sort Chen, Chih-Chieh
collection PubMed
description The new coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been reported and spread globally. There is an urgent need to take urgent measures to treat and prevent further infection of this virus. Here, we use virtual drug screening to establish pharmacophore groups and analyze the ACE2 binding site of the spike protein with the ZINC drug database and DrugBank database by molecular docking and molecular dynamics simulations. Screening results showed that Venetoclax, a treatment drug for chronic lymphocytic leukemia, has a potential ability to bind to the spike protein of SARS-CoV-2. In addition, our in vitro study found that Venetoclax degraded the expression of the spike protein of SARS-CoV-2 through amino acids Q493 and S494 and blocked the interaction with the ACE2 receptor. Our results suggest that Venetoclax is a candidate for clinical prevention and treatment and deserves further research.
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spelling pubmed-92216102022-06-24 Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2 Chen, Chih-Chieh Zhuang, Zhi-Jie Wu, Chia-Wei Tan, Yi-Ling Huang, Chen-Hsiu Hsu, Chia-Yi Tsai, Eing-Mei Hsieh, Tsung-Hua Cells Article The new coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been reported and spread globally. There is an urgent need to take urgent measures to treat and prevent further infection of this virus. Here, we use virtual drug screening to establish pharmacophore groups and analyze the ACE2 binding site of the spike protein with the ZINC drug database and DrugBank database by molecular docking and molecular dynamics simulations. Screening results showed that Venetoclax, a treatment drug for chronic lymphocytic leukemia, has a potential ability to bind to the spike protein of SARS-CoV-2. In addition, our in vitro study found that Venetoclax degraded the expression of the spike protein of SARS-CoV-2 through amino acids Q493 and S494 and blocked the interaction with the ACE2 receptor. Our results suggest that Venetoclax is a candidate for clinical prevention and treatment and deserves further research. MDPI 2022-06-14 /pmc/articles/PMC9221610/ /pubmed/35741053 http://dx.doi.org/10.3390/cells11121924 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Chih-Chieh
Zhuang, Zhi-Jie
Wu, Chia-Wei
Tan, Yi-Ling
Huang, Chen-Hsiu
Hsu, Chia-Yi
Tsai, Eing-Mei
Hsieh, Tsung-Hua
Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2
title Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2
title_full Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2
title_fullStr Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2
title_full_unstemmed Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2
title_short Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2
title_sort venetoclax decreases the expression of the spike protein through amino acids q493 and s494 in sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221610/
https://www.ncbi.nlm.nih.gov/pubmed/35741053
http://dx.doi.org/10.3390/cells11121924
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