Cargando…

The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance

Infectious pandemics result in hundreds and millions of deaths, notable examples of the Spanish Flu, the Black Death and smallpox. The current pandemic, caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is unprecedented even in the historical term of pandemics. The unprecedente...

Descripción completa

Detalles Bibliográficos
Autores principales: Yan, Daisy, Ra, One Hyuk, Yan, Bingfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422062/
https://www.ncbi.nlm.nih.gov/pubmed/34778881
http://dx.doi.org/10.1186/s44149-021-00017-5
_version_ 1783749210404814848
author Yan, Daisy
Ra, One Hyuk
Yan, Bingfang
author_facet Yan, Daisy
Ra, One Hyuk
Yan, Bingfang
author_sort Yan, Daisy
collection PubMed
description Infectious pandemics result in hundreds and millions of deaths, notable examples of the Spanish Flu, the Black Death and smallpox. The current pandemic, caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is unprecedented even in the historical term of pandemics. The unprecedentedness is featured by multiple surges, rapid identification of therapeutic options and accelerated development of vaccines. Remdesivir, originally developed for Ebola viral disease, is the first treatment of COVID-19 (Coronavirus disease 2019) approved by the United States Food and Drug Administration. As demonstrated by in vitro and preclinical studies, this therapeutic agent is highly potent with a broad spectrum activity against viruses from as many as seven families even cross species. However, randomized controlled trials have failed to confirm the efficacy and safety. Remdesivir improves some clinical signs but not critical parameters such as mortality. This antiviral agent is an ester/phosphorylation prodrug and excessive hydrolysis which increases cellular toxicity. Remdesivir is given intravenously, leading to concentration spikes and likely increasing the potential of hydrolysis-based toxicity. This review has proposed a conceptual framework for improving its efficacy and minimizing toxicity not only for the COVID-19 pandemic but also for future ones caused by remdesivir-sensitive viruses.
format Online
Article
Text
id pubmed-8422062
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Springer Singapore
record_format MEDLINE/PubMed
spelling pubmed-84220622021-09-07 The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance Yan, Daisy Ra, One Hyuk Yan, Bingfang Anim Dis Review Infectious pandemics result in hundreds and millions of deaths, notable examples of the Spanish Flu, the Black Death and smallpox. The current pandemic, caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is unprecedented even in the historical term of pandemics. The unprecedentedness is featured by multiple surges, rapid identification of therapeutic options and accelerated development of vaccines. Remdesivir, originally developed for Ebola viral disease, is the first treatment of COVID-19 (Coronavirus disease 2019) approved by the United States Food and Drug Administration. As demonstrated by in vitro and preclinical studies, this therapeutic agent is highly potent with a broad spectrum activity against viruses from as many as seven families even cross species. However, randomized controlled trials have failed to confirm the efficacy and safety. Remdesivir improves some clinical signs but not critical parameters such as mortality. This antiviral agent is an ester/phosphorylation prodrug and excessive hydrolysis which increases cellular toxicity. Remdesivir is given intravenously, leading to concentration spikes and likely increasing the potential of hydrolysis-based toxicity. This review has proposed a conceptual framework for improving its efficacy and minimizing toxicity not only for the COVID-19 pandemic but also for future ones caused by remdesivir-sensitive viruses. Springer Singapore 2021-09-07 2021 /pmc/articles/PMC8422062/ /pubmed/34778881 http://dx.doi.org/10.1186/s44149-021-00017-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Yan, Daisy
Ra, One Hyuk
Yan, Bingfang
The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance
title The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance
title_full The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance
title_fullStr The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance
title_full_unstemmed The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance
title_short The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance
title_sort nucleoside antiviral prodrug remdesivir in treating covid-19 and beyond with interspecies significance
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422062/
https://www.ncbi.nlm.nih.gov/pubmed/34778881
http://dx.doi.org/10.1186/s44149-021-00017-5
work_keys_str_mv AT yandaisy thenucleosideantiviralprodrugremdesivirintreatingcovid19andbeyondwithinterspeciessignificance
AT raonehyuk thenucleosideantiviralprodrugremdesivirintreatingcovid19andbeyondwithinterspeciessignificance
AT yanbingfang thenucleosideantiviralprodrugremdesivirintreatingcovid19andbeyondwithinterspeciessignificance
AT yandaisy nucleosideantiviralprodrugremdesivirintreatingcovid19andbeyondwithinterspeciessignificance
AT raonehyuk nucleosideantiviralprodrugremdesivirintreatingcovid19andbeyondwithinterspeciessignificance
AT yanbingfang nucleosideantiviralprodrugremdesivirintreatingcovid19andbeyondwithinterspeciessignificance