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Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections

Human cytomegalovirus (HCMV) is ubiquitous worldwide and elicits global health problems. The diseases associated with HCMV are a serious threat to humans, especially for the sick, infant, elderly and immunocompromised/immunodeficient individuals. Although traditional antiviral drugs (e.g., ganciclov...

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Autores principales: Chen, Shiu-Jau, Wang, Shao-Cheng, Chen, Yuan-Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9784992/
https://www.ncbi.nlm.nih.gov/pubmed/36548694
http://dx.doi.org/10.3390/tropicalmed7120439
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author Chen, Shiu-Jau
Wang, Shao-Cheng
Chen, Yuan-Chuan
author_facet Chen, Shiu-Jau
Wang, Shao-Cheng
Chen, Yuan-Chuan
author_sort Chen, Shiu-Jau
collection PubMed
description Human cytomegalovirus (HCMV) is ubiquitous worldwide and elicits global health problems. The diseases associated with HCMV are a serious threat to humans, especially for the sick, infant, elderly and immunocompromised/immunodeficient individuals. Although traditional antiviral drugs (e.g., ganciclovir, valganciclovir, cidofovir, foscarnet) can be used to treat or prevent acute HCMV infections, their efficacy is limited because of toxicity, resistance issues, side effects and other problems. Fortunately, novel drugs (e.g., letermovir and maribavir) with less toxicity and drug/cross-resistance have been approved and put on the market in recent years. The nucleic acid-based gene-targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPRs-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) have been investigated to remove both lytic and latent CMV in vitro and/or in vivo. Cell therapy including the adoptive T cell therapy (ACT) and immunotherapy have been tried against drug-resistant and recurrent HCMV in patients receiving hematopoietic stem cell transplantation (HSCT) or solid organ transplant (SOT), and they have also been used to treat glioblastoma (GBM) associated with HCMV infections. These newly developed antiviral strategies are expected to yield fruitful results and make a significant contribution to the treatment of HCMV infections. Despite this progress, the nucleic acid-based gene-targeting approaches are still under study for basic research, and cell therapy is adopted in a small study population size or only successful in case reports. Additionally, no current drugs have been approved to be indicated for latent infections. Therefore, the next strategy is to develop antiviral strategies to elevate efficacy against acute and/or latent infections and overcome challenges such as toxicity, resistance issues, and side effects. In this review, we would explore the challenges, recent advances and perspectives in the treatment of HCMV infections. Furthermore, the suitable therapeutic strategies as well as the possibility for compassionate use would be evaluated.
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spelling pubmed-97849922022-12-24 Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections Chen, Shiu-Jau Wang, Shao-Cheng Chen, Yuan-Chuan Trop Med Infect Dis Review Human cytomegalovirus (HCMV) is ubiquitous worldwide and elicits global health problems. The diseases associated with HCMV are a serious threat to humans, especially for the sick, infant, elderly and immunocompromised/immunodeficient individuals. Although traditional antiviral drugs (e.g., ganciclovir, valganciclovir, cidofovir, foscarnet) can be used to treat or prevent acute HCMV infections, their efficacy is limited because of toxicity, resistance issues, side effects and other problems. Fortunately, novel drugs (e.g., letermovir and maribavir) with less toxicity and drug/cross-resistance have been approved and put on the market in recent years. The nucleic acid-based gene-targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPRs-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) have been investigated to remove both lytic and latent CMV in vitro and/or in vivo. Cell therapy including the adoptive T cell therapy (ACT) and immunotherapy have been tried against drug-resistant and recurrent HCMV in patients receiving hematopoietic stem cell transplantation (HSCT) or solid organ transplant (SOT), and they have also been used to treat glioblastoma (GBM) associated with HCMV infections. These newly developed antiviral strategies are expected to yield fruitful results and make a significant contribution to the treatment of HCMV infections. Despite this progress, the nucleic acid-based gene-targeting approaches are still under study for basic research, and cell therapy is adopted in a small study population size or only successful in case reports. Additionally, no current drugs have been approved to be indicated for latent infections. Therefore, the next strategy is to develop antiviral strategies to elevate efficacy against acute and/or latent infections and overcome challenges such as toxicity, resistance issues, and side effects. In this review, we would explore the challenges, recent advances and perspectives in the treatment of HCMV infections. Furthermore, the suitable therapeutic strategies as well as the possibility for compassionate use would be evaluated. MDPI 2022-12-14 /pmc/articles/PMC9784992/ /pubmed/36548694 http://dx.doi.org/10.3390/tropicalmed7120439 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 Review
Chen, Shiu-Jau
Wang, Shao-Cheng
Chen, Yuan-Chuan
Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections
title Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections
title_full Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections
title_fullStr Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections
title_full_unstemmed Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections
title_short Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections
title_sort challenges, recent advances and perspectives in the treatment of human cytomegalovirus infections
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9784992/
https://www.ncbi.nlm.nih.gov/pubmed/36548694
http://dx.doi.org/10.3390/tropicalmed7120439
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