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

作　　者：Daisy Yan One Hyuk Ra Bingfang Yan 

机构地区：[1]Sidney Kimmel Medical College,Thomas Jefferson University,1025 Walnut St,Philadelphia,PA 19107,USA [2]Department of Anesthesiology,Brigham and Women's Hospital,75 Francis St,Boston,MA 02115,USA [3]Division of Pharmaceutical Sciences,James L Winkle College of Pharmacy,University of Cincinnati,Cincinnati,OH 45229,USA

出　　处：《Animal Diseases》2022年第1期1-15,共15页动物疾病（英文）

基　　金：supported by National Institutes of Health Grants R01 EB018748,R21 Al153031;University of Cincinnati Cancer Center(Yan,B).

摘　　要：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.

关 键 词：Animal model CARBOXYLESTERASES COVID-19 CORONAVIRUS Drug-drug interactions interspecies difference Pandemic Remdesivir SARS-CoV-2 

分 类 号：R51[医药卫生—内科学]