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Tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for COVID‐19
Several human host proteins play important roles in the lifecycle of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Many drugs targeting these host proteins have been investigated as potential therapeutics for coronavirus disease 2019 (COVID‐19). The tissue‐specific expressions of sel...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747131/ https://www.ncbi.nlm.nih.gov/pubmed/36259251 http://dx.doi.org/10.1111/cts.13400 |
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author | Li, Jiapeng Xue, Yanling Wang, Xinwen Smith, Logan S. He, Bing Liu, Shuhan Zhu, Hao‐Jie |
author_facet | Li, Jiapeng Xue, Yanling Wang, Xinwen Smith, Logan S. He, Bing Liu, Shuhan Zhu, Hao‐Jie |
author_sort | Li, Jiapeng |
collection | PubMed |
description | Several human host proteins play important roles in the lifecycle of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Many drugs targeting these host proteins have been investigated as potential therapeutics for coronavirus disease 2019 (COVID‐19). The tissue‐specific expressions of selected host proteins were summarized using proteomics data retrieved from the Human Protein Atlas, ProteomicsDB, Human Proteome Map databases, and a clinical COVID‐19 study. Protein expression features in different cell lines were summarized based on recent proteomics studies. The half‐maximal effective concentration or half‐maximal inhibitory concentration values were collected from in vitro studies. The pharmacokinetic data were mainly from studies in healthy subjects or non‐COVID‐19 patients. Considerable tissue‐specific expression patterns were observed for several host proteins. ACE2 expression in the lungs was significantly lower than in many other tissues (e.g., the kidneys and intestines); TMPRSS2 expression in the lungs was significantly lower than in other tissues (e.g., the prostate and intestines). The expression levels of endocytosis‐associated proteins CTSL, CLTC, NPC1, and PIKfyve in the lungs were comparable to or higher than most other tissues. TMPRSS2 expression was markedly different between cell lines, which could be associated with the cell‐dependent antiviral activities of several drugs. Drug delivery receptor ICAM1 and CTSB were expressed at a higher level in the lungs than in other tissues. In conclusion, the cell‐ and tissue‐specific proteomics data could help interpret the in vitro antiviral activities of host‐directed drugs in various cells and aid the transition of the in vitro findings to clinical research to develop safe and effective therapeutics for COVID‐19. |
format | Online Article Text |
id | pubmed-9747131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97471312022-12-14 Tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for COVID‐19 Li, Jiapeng Xue, Yanling Wang, Xinwen Smith, Logan S. He, Bing Liu, Shuhan Zhu, Hao‐Jie Clin Transl Sci Reviews Several human host proteins play important roles in the lifecycle of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Many drugs targeting these host proteins have been investigated as potential therapeutics for coronavirus disease 2019 (COVID‐19). The tissue‐specific expressions of selected host proteins were summarized using proteomics data retrieved from the Human Protein Atlas, ProteomicsDB, Human Proteome Map databases, and a clinical COVID‐19 study. Protein expression features in different cell lines were summarized based on recent proteomics studies. The half‐maximal effective concentration or half‐maximal inhibitory concentration values were collected from in vitro studies. The pharmacokinetic data were mainly from studies in healthy subjects or non‐COVID‐19 patients. Considerable tissue‐specific expression patterns were observed for several host proteins. ACE2 expression in the lungs was significantly lower than in many other tissues (e.g., the kidneys and intestines); TMPRSS2 expression in the lungs was significantly lower than in other tissues (e.g., the prostate and intestines). The expression levels of endocytosis‐associated proteins CTSL, CLTC, NPC1, and PIKfyve in the lungs were comparable to or higher than most other tissues. TMPRSS2 expression was markedly different between cell lines, which could be associated with the cell‐dependent antiviral activities of several drugs. Drug delivery receptor ICAM1 and CTSB were expressed at a higher level in the lungs than in other tissues. In conclusion, the cell‐ and tissue‐specific proteomics data could help interpret the in vitro antiviral activities of host‐directed drugs in various cells and aid the transition of the in vitro findings to clinical research to develop safe and effective therapeutics for COVID‐19. John Wiley and Sons Inc. 2022-10-19 2022-12 /pmc/articles/PMC9747131/ /pubmed/36259251 http://dx.doi.org/10.1111/cts.13400 Text en © 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Reviews Li, Jiapeng Xue, Yanling Wang, Xinwen Smith, Logan S. He, Bing Liu, Shuhan Zhu, Hao‐Jie Tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for COVID‐19 |
title | Tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for COVID‐19 |
title_full | Tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for COVID‐19 |
title_fullStr | Tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for COVID‐19 |
title_full_unstemmed | Tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for COVID‐19 |
title_short | Tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for COVID‐19 |
title_sort | tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for covid‐19 |
topic | Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747131/ https://www.ncbi.nlm.nih.gov/pubmed/36259251 http://dx.doi.org/10.1111/cts.13400 |
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