Article
Microbiology
E. Leegwater, D. J. A. R. Moes, L. B. E. Bosma, T. H. Ottens, I. M. van der Meer, C. van Nieuwkoop, E. B. Wilms
Summary: This study aimed to investigate the pharmacokinetics of remdesivir and GS-441524 in hospitalized COVID-19 patients. The clearance of GS-441524 was found to be dependent on the eGFR, with high interindividual variability. The short elimination half-life of remdesivir in COVID-19 patients and the accumulation of GS-441524 in patients with reduced renal function were observed. Alternative dosing regimens may improve the effectiveness of remdesivir treatment in COVID-19 patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Massimo Tempestilli, Tommaso Ascoli Bartoli, Domenico Benvenuto, Giulia Valeria Stazi, Luisa Marchioni, Emanuele Nicastri, Chiara Agrati
Summary: This study aimed to investigate the inter-individual variability of remdesivir and its metabolite GS-441524 in COVID-19 inpatients and its associations with demographic/biochemical variables. The results showed a high interpatient variability of remdesivir and GS-441524, likely influenced by age and renal function in COVID-19 inpatients.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Yuki Nakano, Yoko Inokuchi, Tadashi Hayama, Toshinori Hirai, Mamoru Nishiyama, Yoshiko Sueyasu, Kenjo Yokoo
Summary: This study aimed to determine the effective concentration of GS-441524, a key drug for treating COVID-19 pneumonia. The research found that there is a correlation between the concentration of GS-441524 and the improvement of COVID-19 pneumonia symptoms, and a concentration above 70 ng/mL can effectively predict efficacy. Decreased estimated glomerular filtration rate and BMI over 25 kg/m 2 were found to affect the probability of achieving effective concentration.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Multidisciplinary Sciences
Robert M. Cox, Josef D. Wolf, Carolin M. Lieber, Julien Sourimant, Michelle J. Lin, Darius Babusis, Venice DuPont, Julie Chan, Kim T. Barrett, Diane Lye, Rao Kalla, Kwon Chun, Richard L. Mackman, Chengjin Ye, Tomas Cihlar, Luis Martinez-Sobrido, Alexander L. Greninger, John P. Bilello, Richard K. Plemper
Summary: Remdesivir is an antiviral drug approved for COVID-19 treatment, but its intravenous administration limits wider use. A study has shown that GS-621763, an oral prodrug of remdesivir parent nucleoside GS-441524, has good oral bioavailability and inhibits SARS-CoV-2 and variants of concern in ferrets, demonstrating therapeutic efficacy in a relevant animal model of SARS-CoV-2 infection.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Ramkumar Moorthy, Samantha A. Kennelly, Deborah J. Rodriguez, Daniel A. Harki
Summary: An efficient synthesis of the phosphoramidite of GS-441524, the nucleoside precursor of remdesivir, was reported for studies of viral polymerases with RNA containing remdesivir.
Article
Medicine, General & Internal
Ling Yang, I-Hsin Lin, Lie-Chwen Lin, Jeffrey W. Dalley, Tung-Hu Tsai
Summary: This study demonstrates through experiments that remdesivir and its main metabolite, GS-441524, can cross the placenta, but remdesivir itself cannot directly enter the fetus. This finding suggests that caution should be taken when using remdesivir to treat COVID-19 during pregnancy.
Review
Immunology
Zhonglei Wang, Liyan Yang, Xian-qing Song
Summary: This review summarizes the research related to the oral derivatives of GS-441524 and provides important insights into the controversial observations regarding the clinical efficacy. Oral GS-441524 derivatives could be considered as significant breakthroughs in treating COVID-19 due to their potential for maximizing clinical benefits.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Jared Pitts, Jiani Li, Jason K. Perry, Venice Du Pont, Nicholas Riola, Lauren Rodriguez, Xianghan Lu, Chaitanya Kurhade, Xuping Xie, Gregory Camus, Savrina Manhas, Ross Martin, Pei-Yong Shi, Tomas Cihlar, Danielle P. Porter, Hongmei Mo, Evguenia Maiorova, John P. Bilello
Summary: Genetic variation of SARS-CoV-2 has led to the emergence and rapid spread of multiple variants, including Omicron. This study assessed the antiviral activity of Remdesivir and its parent nucleoside, GS-441524, against various SARS-CoV-2 variants. The results showed that Delta and Omicron variants remained susceptible to Remdesivir and GS-441524, while other variants exhibited varied susceptibility.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemical Research Methods
Deqing Xiao, Kah Hiing John Ling, Thomas Tarnowski, Rita Humeniuk, Polina German, Anita Mathias, Jasper Chu, Yuan-Shek Chen, Eric van Ingen
Summary: This study validated LC-MS/MS methods for the determination of three analytes in human plasma, overcoming instability issues through diluted formic acid treatment and separate injections. The method demonstrated high precision and accuracy, with successful application in COVID-19 related clinical studies.
ANALYTICAL BIOCHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Asami Sukeishi, Kotaro Itohara, Atsushi Yonezawa, Yuki Sato, Katsuyuki Matsumura, Yoshiki Katada, Takayuki Nakagawa, Satoshi Hamada, Naoya Tanabe, Eishi Imoto, Shinichi Kai, Toyohiro Hirai, Motoko Yanagita, Shigeru Ohtsuru, Tomohiro Terada, Isao Ito
Summary: In this study, a population PK model of GS-441524 was successfully established using serum concentrations obtained from Japanese patients with COVID-19. The study proposed a dose regimen of remdesivir for patients with an eGFR of 30 ml/min or less based on the analysis. This model could aid in optimizing individualized therapy of remdesivir.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Amy Q. Q. Wang, Natalie R. R. Hagen, Elias C. C. Padilha, Mengbi Yang, Pranav Shah, Catherine Z. Z. Chen, Wenwei Huang, Pramod Terse, Philip Sanderson, Wei Zheng, Xin Xu
Summary: The preclinical pharmacokinetics and in vitro ADME properties of GS-441524, a potential oral drug for Covid-19 treatment, were studied. The results showed that GS-441524 had good stability and distribution in various species, and it was found to be a substrate for specific transporters. The drug was primarily eliminated through urine, and it exhibited high oral bioavailability. These findings support the further development of GS-441524 as an oral drug candidate.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Engineering, Biomedical
Carina E. Imburgia, Joseph E. Rower, Danielle J. Green, Autumn M. Mcknite, Walter E. Kelley, Christopher A. Reilly, Kevin M. Watt
Summary: The study found significant drug loss of RDV and its metabolite in ECMO and CRRT circuits, mainly due to drug adsorption by circuit materials or efficient hemodiafiltration.
Review
Virology
Henrik Berg Rasmussen, Gesche Jurgens, Ragnar Thomsen, Olivier Taboureau, Kornelius Zeth, Poul Erik Hansen, Peter Riis Hansen
Summary: GS-441524 is a potential treatment for COVID-19 and its efficacy relies on cellular uptake and conversion processes, which may be impacted by tissue hypoxia and inflammation. This could lead to reduced therapeutic effectiveness of GS-441524 in treating COVID-19.
Article
Pharmacology & Pharmacy
Jiashu Xie, Zhengqiang Wang
Summary: The study examined the potential of Remdesivir and its parent nucleoside GS-441524 as oral drugs for treating COVID-19. Results showed that Remdesivir had poor stability in vitro, while GS-441524 exhibited better metabolic stability and oral bioavailability, indicating its potential as a promising oral antiviral drug for COVID-19 treatment.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Pharmacology & Pharmacy
Dinesh S. Moirangthem, Laishram Surbala
Summary: COVID-19, caused by SARS-CoV-2, has led to a global pandemic. Remdesivir, a potential antiviral drug undergoing clinical trials, has shown promise in treating severe cases of the disease.
CURRENT DRUG TARGETS
(2021)
Article
Reproductive Biology
Lei Gong, Siyi Jiang, Jia Tian, Yong Li, Wansu Yu, Lubo Zhang, Daliao Xiao
Summary: Exposure to gestational diabetes mellitus during pregnancy can lead to the development of a neonatal brain hypoxia/ischemia-sensitive phenotype. The PTEN/AKT/mTOR/autophagy signaling pathway plays a role in this process.
REPRODUCTIVE TOXICOLOGY
(2024)
Article
Reproductive Biology
Sudipta Dutta, Kirthiram K. Sivakumar, John W. Erwin, Jone A. Stanley, Joe A. Arosh, Robert J. Taylor, Sakhila K. Banu
Summary: This study found that exposure to hexavalent chromium disrupts follicle development and causes apoptosis by altering epigenetic marks in the ovary.
REPRODUCTIVE TOXICOLOGY
(2024)
Article
Reproductive Biology
Yuxin Li, Xianzhi He, Bin Sun, Nannan Hu, Jiamin Li, Ruolan You, Feiyan Tao, Lei Fang, Yuanyuan Li, Qingfeng Zhai
Summary: This study investigated the toxic effects and mechanism of beta-CYP and EMB on the reproductive system of female rats. The results showed that exposure to these pesticides led to changes in hormone and gene expression in the hypothalamic-pituitary-ovarian axis, as well as alterations in oxidative damage indicators. The findings support the evaluation of the adverse effects of pesticide exposure on reproductive health in greenhouse operations.
REPRODUCTIVE TOXICOLOGY
(2024)
Article
Reproductive Biology
Ran Lee, Won-Young Lee, Hyun-Jung Park
Summary: This study investigates the toxicity of diuron on fetal mouse testes and finds that diuron has a negative impact on the development of fetal Leydig cells, while not affecting germ cells and Sertoli cells.
REPRODUCTIVE TOXICOLOGY
(2024)