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Investigating Derivatives of Tanshinone IIA Sulfonate Sodium and Chloroxine for Their Inhibition Activities against the SARS-CoV-2 Papain-like Protease
[Image: see text] SARS-CoV-2 has caused a global pandemic of COVID-19, posing a huge threat to public health. The SARS-CoV-2 papain-like cysteine protease (PLpro) plays a significant role in virus replication and host immune regulation, which is a promising antiviral drug target. Several potential i...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798770/ https://www.ncbi.nlm.nih.gov/pubmed/36591160 http://dx.doi.org/10.1021/acsomega.2c06675 |
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author | Chen, Xin Chen, Ke Zhang, Zhaoyong Wei, Peilan Zhang, Lu Xu, Yunxia Lun, Qili Ma, Yanhong Wu, Fang Zhang, Ying Wang, Yanqun Zhao, Jincun Zhou, Yaoqi Zhan, Jian Xu, Wei |
author_facet | Chen, Xin Chen, Ke Zhang, Zhaoyong Wei, Peilan Zhang, Lu Xu, Yunxia Lun, Qili Ma, Yanhong Wu, Fang Zhang, Ying Wang, Yanqun Zhao, Jincun Zhou, Yaoqi Zhan, Jian Xu, Wei |
author_sort | Chen, Xin |
collection | PubMed |
description | [Image: see text] SARS-CoV-2 has caused a global pandemic of COVID-19, posing a huge threat to public health. The SARS-CoV-2 papain-like cysteine protease (PLpro) plays a significant role in virus replication and host immune regulation, which is a promising antiviral drug target. Several potential inhibitors have been identified in vitro. However, the detailed mechanism of action and structure–activity relationship require further studies. Here, we investigated the structure–activity relationships of the series of derivatives of tanshinone IIA sulfonate sodium (TSS) and chloroxine based on biochemical analysis and molecular dynamics simulation. We found that compound 7, a derivative of chloroxine, can disrupt PLpro-ISG15 interaction and exhibits an antiviral effect for SARS-CoV-2 variants (wild type, delta, and omicron) at the low micromolar level. These studies confirmed that inhibiting PLpro-ISG15 interaction and, thus, restoring the host’s innate immunity are effective methods for fighting against viral infection. |
format | Online Article Text |
id | pubmed-9798770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-97987702022-12-30 Investigating Derivatives of Tanshinone IIA Sulfonate Sodium and Chloroxine for Their Inhibition Activities against the SARS-CoV-2 Papain-like Protease Chen, Xin Chen, Ke Zhang, Zhaoyong Wei, Peilan Zhang, Lu Xu, Yunxia Lun, Qili Ma, Yanhong Wu, Fang Zhang, Ying Wang, Yanqun Zhao, Jincun Zhou, Yaoqi Zhan, Jian Xu, Wei ACS Omega [Image: see text] SARS-CoV-2 has caused a global pandemic of COVID-19, posing a huge threat to public health. The SARS-CoV-2 papain-like cysteine protease (PLpro) plays a significant role in virus replication and host immune regulation, which is a promising antiviral drug target. Several potential inhibitors have been identified in vitro. However, the detailed mechanism of action and structure–activity relationship require further studies. Here, we investigated the structure–activity relationships of the series of derivatives of tanshinone IIA sulfonate sodium (TSS) and chloroxine based on biochemical analysis and molecular dynamics simulation. We found that compound 7, a derivative of chloroxine, can disrupt PLpro-ISG15 interaction and exhibits an antiviral effect for SARS-CoV-2 variants (wild type, delta, and omicron) at the low micromolar level. These studies confirmed that inhibiting PLpro-ISG15 interaction and, thus, restoring the host’s innate immunity are effective methods for fighting against viral infection. American Chemical Society 2022-12-12 /pmc/articles/PMC9798770/ /pubmed/36591160 http://dx.doi.org/10.1021/acsomega.2c06675 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Chen, Xin Chen, Ke Zhang, Zhaoyong Wei, Peilan Zhang, Lu Xu, Yunxia Lun, Qili Ma, Yanhong Wu, Fang Zhang, Ying Wang, Yanqun Zhao, Jincun Zhou, Yaoqi Zhan, Jian Xu, Wei Investigating Derivatives of Tanshinone IIA Sulfonate Sodium and Chloroxine for Their Inhibition Activities against the SARS-CoV-2 Papain-like Protease |
title | Investigating Derivatives
of Tanshinone IIA Sulfonate
Sodium and Chloroxine for Their Inhibition Activities against the
SARS-CoV-2 Papain-like Protease |
title_full | Investigating Derivatives
of Tanshinone IIA Sulfonate
Sodium and Chloroxine for Their Inhibition Activities against the
SARS-CoV-2 Papain-like Protease |
title_fullStr | Investigating Derivatives
of Tanshinone IIA Sulfonate
Sodium and Chloroxine for Their Inhibition Activities against the
SARS-CoV-2 Papain-like Protease |
title_full_unstemmed | Investigating Derivatives
of Tanshinone IIA Sulfonate
Sodium and Chloroxine for Their Inhibition Activities against the
SARS-CoV-2 Papain-like Protease |
title_short | Investigating Derivatives
of Tanshinone IIA Sulfonate
Sodium and Chloroxine for Their Inhibition Activities against the
SARS-CoV-2 Papain-like Protease |
title_sort | investigating derivatives
of tanshinone iia sulfonate
sodium and chloroxine for their inhibition activities against the
sars-cov-2 papain-like protease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798770/ https://www.ncbi.nlm.nih.gov/pubmed/36591160 http://dx.doi.org/10.1021/acsomega.2c06675 |
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