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Probenecid Inhibits Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase Mitogen-Activated Protein Kinase Pathways in Regulating Respiratory Syncytial Virus Response.
Int J Mol Sci
November 2024
Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
Unlabelled: We examined the effect of probenecid in regulating the ERK and JNK downstream MAPK pathways affecting respiratory syncytial virus replication.
Background: We have previously shown that probenecid inhibits RSV, influenza virus, and SARS-CoV-2 replication in vitro in preclinical animal models and in humans. In a Phase two randomized, placebo-controlled, single-blind, dose range-finding study using probenecid to treat non-hospitalized patients with symptomatic, mild-to-moderate COVID-19, we previously showed that a 1000 mg twice daily treatment for 5 days reduced the median time to viral clearance from 11 to 7 days, and a 500 mg twice daily treatment for 5 days reduced the time to viral clearance from 11 to 9 days more than the placebo.
A phase 3 randomized trial of sulopenem vs. ertapenem in patients with complicated intra-abdominal infections.
Clin Microbiol Infect
November 2024
Boston, MA, USA.
Article Synopsis
- - The study aimed to compare the effectiveness of intravenous sulopenem with intravenous ertapenem, both followed by oral treatments, in treating complicated intra-abdominal infections (cIAI) in hospitalized adults.
- - A total of 674 patients were enrolled, showing clinical success rates of 81.9% for sulopenem and 87.9% for ertapenem, indicating that sulopenem was not as effective as ertapenem within the predefined non-inferiority margin.
- - Adverse events were similar between the two treatments, with more serious adverse effects noted in the sulopenem group; however, most side effects were mild to moderate in severity.
Discovery of a Potent and Orally Bioavailable Xanthine Oxidase/Urate Transporter 1 Dual Inhibitor as a Potential Treatment for Hyperuricemia and Gout.
J Med Chem
August 2024
Laboratory of Drug Design and Discovery, Department of Chemistry, China Pharmaceutical University, Nanjing 211198, China.
Article Synopsis
- - The main treatments for hyperuricemia and gout are xanthine oxidase (XO) inhibitors and urate transporter 1 (URAT1) inhibitors, but these have limitations in effectiveness and safety.
- - Researchers developed a new dual inhibitor that targets both XO and URAT1 to potentially improve treatment outcomes and reduce toxicity.
- - This new compound showed strong inhibition of both targets and favorable safety profiles in animal studies, making it a promising candidate for gout treatment.
Probenecid Inhibits Human Metapneumovirus (HMPV) Replication In Vitro and in BALB/c Mice.
Viruses
July 2024
Department of Infectious Diseases, University of Georgia, Athens, GA 30605, USA.
Human metapneumovirus (HMPV) is an important cause of acute respiratory tract infection and causes significant morbidity and mortality. There is no specific antiviral drug to treat HMPV or vaccine to prevent HMPV. This study determined if probenecid, a host-targeting antiviral drug, had prophylactic (pre-virus) or therapeutic (post-virus) efficacy to inhibit HMPV replication in LLC-MK2 cells in vitro and in the lungs of BALB/c mice.
View Article and Find Full Text PDFOral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19.
Viruses
July 2023
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Probenecid is an orally bioavailable, uricosuric agent that was first approved in 1951 for the treatment of gout, but was later found to have potent, broad-spectrum antiviral activity against several respiratory viruses including SARS-CoV-2. We conducted a phase 2 randomized, placebo-controlled, single-blind, dose-range finding study in non-hospitalized patients with symptomatic, mild-to-moderate COVID-19. Patients were randomly assigned in a 1:1:1 ratio to receive either 500 mg of probenecid, 1000 mg of probenecid, or a matching placebo every 12 h for five days.
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