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A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 (COVID-19). Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2...

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Autores principales: Tong, Liangqin, Wang, Lin, Liao, Shumin, Xiao, Xiaoping, Qu, Jing, Wu, Chunli, Zhu, Yibin, Tai, Wanbo, Huang, Yanhong, Wang, Penghua, Li, Liang, Zhang, Renli, Xiang, Ye, Cheng, Gong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426596/
https://www.ncbi.nlm.nih.gov/pubmed/35862773
http://dx.doi.org/10.1128/mbio.01485-22
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author Tong, Liangqin
Wang, Lin
Liao, Shumin
Xiao, Xiaoping
Qu, Jing
Wu, Chunli
Zhu, Yibin
Tai, Wanbo
Huang, Yanhong
Wang, Penghua
Li, Liang
Zhang, Renli
Xiang, Ye
Cheng, Gong
author_facet Tong, Liangqin
Wang, Lin
Liao, Shumin
Xiao, Xiaoping
Qu, Jing
Wu, Chunli
Zhu, Yibin
Tai, Wanbo
Huang, Yanhong
Wang, Penghua
Li, Liang
Zhang, Renli
Xiang, Ye
Cheng, Gong
author_sort Tong, Liangqin
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 (COVID-19). Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2 variants. Here, we found that all-trans retinoic acid (ATRA), a vitamin A (retinol) derivative, showed potent antiviral activity against all SARS-CoV-2 variants in both human cell lines and human organoids of the lower respiratory tract. Mechanistically, ATRA directly binds in a deep hydrophobic pocket of the receptor binding domain (RBD) located on the top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the “down” RBDs and locks most of the S trimers in an RBD “all-down” and ACE2-inaccessible inhibitory conformation. In summary, our results reveal the pharmacological biotargets and structural mechanism of ATRA and other retinoids in SARS-CoV-2 infection and suggest that ATRA and its derivatives could be potential hit compounds against a broad spectrum of coronaviruses.
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spelling pubmed-94265962022-08-31 A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry Tong, Liangqin Wang, Lin Liao, Shumin Xiao, Xiaoping Qu, Jing Wu, Chunli Zhu, Yibin Tai, Wanbo Huang, Yanhong Wang, Penghua Li, Liang Zhang, Renli Xiang, Ye Cheng, Gong mBio Research Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 (COVID-19). Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2 variants. Here, we found that all-trans retinoic acid (ATRA), a vitamin A (retinol) derivative, showed potent antiviral activity against all SARS-CoV-2 variants in both human cell lines and human organoids of the lower respiratory tract. Mechanistically, ATRA directly binds in a deep hydrophobic pocket of the receptor binding domain (RBD) located on the top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the “down” RBDs and locks most of the S trimers in an RBD “all-down” and ACE2-inaccessible inhibitory conformation. In summary, our results reveal the pharmacological biotargets and structural mechanism of ATRA and other retinoids in SARS-CoV-2 infection and suggest that ATRA and its derivatives could be potential hit compounds against a broad spectrum of coronaviruses. American Society for Microbiology 2022-07-13 /pmc/articles/PMC9426596/ /pubmed/35862773 http://dx.doi.org/10.1128/mbio.01485-22 Text en Copyright © 2022 Tong et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Tong, Liangqin
Wang, Lin
Liao, Shumin
Xiao, Xiaoping
Qu, Jing
Wu, Chunli
Zhu, Yibin
Tai, Wanbo
Huang, Yanhong
Wang, Penghua
Li, Liang
Zhang, Renli
Xiang, Ye
Cheng, Gong
A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry
title A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry
title_full A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry
title_fullStr A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry
title_full_unstemmed A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry
title_short A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry
title_sort retinol derivative inhibits sars-cov-2 infection by interrupting spike-mediated cellular entry
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426596/
https://www.ncbi.nlm.nih.gov/pubmed/35862773
http://dx.doi.org/10.1128/mbio.01485-22
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