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

Abstract 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 unp...

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Autores principales:	Daisy Yan, One Hyuk Ra, Bingfang Yan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Animal model Carboxylesterases COVID-19 Coronavirus Drug-drug interactions, interspecies difference Pandemic Veterinary medicine SF600-1100 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/e47fb334156e4510940dc8ee721837eb
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spelling	oai:doaj.org-article:e47fb334156e4510940dc8ee721837eb2021-11-14T12:06:06ZThe nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance10.1186/s44149-021-00017-52731-0442https://doaj.org/article/e47fb334156e4510940dc8ee721837eb2021-09-01T00:00:00Zhttps://doi.org/10.1186/s44149-021-00017-5https://doaj.org/toc/2731-0442Abstract 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.Daisy YanOne Hyuk RaBingfang YanBMCarticleAnimal modelCarboxylesterasesCOVID-19CoronavirusDrug-drug interactions, interspecies differencePandemicVeterinary medicineSF600-1100Public aspects of medicineRA1-1270ENAnimal Diseases, Vol 1, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Animal model Carboxylesterases COVID-19 Coronavirus Drug-drug interactions, interspecies difference Pandemic Veterinary medicine SF600-1100 Public aspects of medicine RA1-1270
spellingShingle	Animal model Carboxylesterases COVID-19 Coronavirus Drug-drug interactions, interspecies difference Pandemic Veterinary medicine SF600-1100 Public aspects of medicine RA1-1270 Daisy Yan One Hyuk Ra Bingfang Yan The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance
description	Abstract 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	article
author	Daisy Yan One Hyuk Ra Bingfang Yan
author_facet	Daisy Yan One Hyuk Ra Bingfang Yan
author_sort	Daisy Yan
title	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_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_sort	nucleoside antiviral prodrug remdesivir in treating covid-19 and beyond with interspecies significance
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e47fb334156e4510940dc8ee721837eb
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The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance

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