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Cyclophilin A as a target in the treatment of cytomegalovirus infections

BACKGROUND: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that med...

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Autores principales: A Abdullah, Ashwaq, Abdullah, Rasedee, A Nazariah, Zeenathul, N Balakrishnan, Krishnan, Firdaus J Abdullah, Faez, A Bala, Jamilu, Mohd-Lila, Mohd-Azmi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243413/
https://www.ncbi.nlm.nih.gov/pubmed/30449131
http://dx.doi.org/10.1177/2040206618811413
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author A Abdullah, Ashwaq
Abdullah, Rasedee
A Nazariah, Zeenathul
N Balakrishnan, Krishnan
Firdaus J Abdullah, Faez
A Bala, Jamilu
Mohd-Lila, Mohd-Azmi
author_facet A Abdullah, Ashwaq
Abdullah, Rasedee
A Nazariah, Zeenathul
N Balakrishnan, Krishnan
Firdaus J Abdullah, Faez
A Bala, Jamilu
Mohd-Lila, Mohd-Azmi
author_sort A Abdullah, Ashwaq
collection PubMed
description BACKGROUND: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity. METHODS: Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins. RESULTS: Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug. CONCLUSION: Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.
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spelling pubmed-62434132018-11-26 Cyclophilin A as a target in the treatment of cytomegalovirus infections A Abdullah, Ashwaq Abdullah, Rasedee A Nazariah, Zeenathul N Balakrishnan, Krishnan Firdaus J Abdullah, Faez A Bala, Jamilu Mohd-Lila, Mohd-Azmi Antivir Chem Chemother Review BACKGROUND: Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity. METHODS: Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins. RESULTS: Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug. CONCLUSION: Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway. SAGE Publications 2018-11-18 /pmc/articles/PMC6243413/ /pubmed/30449131 http://dx.doi.org/10.1177/2040206618811413 Text en © The Author(s) 2018 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
A Abdullah, Ashwaq
Abdullah, Rasedee
A Nazariah, Zeenathul
N Balakrishnan, Krishnan
Firdaus J Abdullah, Faez
A Bala, Jamilu
Mohd-Lila, Mohd-Azmi
Cyclophilin A as a target in the treatment of cytomegalovirus infections
title Cyclophilin A as a target in the treatment of cytomegalovirus infections
title_full Cyclophilin A as a target in the treatment of cytomegalovirus infections
title_fullStr Cyclophilin A as a target in the treatment of cytomegalovirus infections
title_full_unstemmed Cyclophilin A as a target in the treatment of cytomegalovirus infections
title_short Cyclophilin A as a target in the treatment of cytomegalovirus infections
title_sort cyclophilin a as a target in the treatment of cytomegalovirus infections
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243413/
https://www.ncbi.nlm.nih.gov/pubmed/30449131
http://dx.doi.org/10.1177/2040206618811413
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