GS-441524 / Copycat Sci - LARVOL DELTA

Treatment with subcutaneous GS-441524 in ferrets affected by ferret systemic coronavirus-associated disease: seven cases (2021-2024). (PubMed, J Small Anim Pract) - "This study suggests injectable GS-441524 could be an effective treatment to improve the clinical status, haematological parameters and survival times of ferrets affected with ferret systemic coronavirus-associated disease."

Journal • CNS Disorders • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease

Pharmacokinetics and Metabolism of Broad-Spectrum Antivirals Remdesivir and Obeldesivir with a Consideration to Metabolite GS-441524: Same, Similar, or Different? (PubMed, Viruses) - "The distinct route of administration and metabolic fate of each prodrug produced in vivo PK and metabolism profiles with differential GS-441524 to tissue GS-443902 relationships, thereby supporting alternate methods for predicting human efficacious doses. Overall, a metabolism-directed prodrug design enabled optimized delivery of the identical active GS-443902 metabolite through different routes of administration, supporting broader applications of the same nucleoside analog across an expanded spectrum of potential antiviral indications."

Journal • PK/PD data • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

Eco-friendly spectrofluorimetric determination of remdesivir in the presence of its metabolite in human plasma for therapeutic monitoring in COVID-19 patients. (PubMed, Sci Rep) - "A selective and sensitive derivative spectrofluorimetric method has been developed and validated for the determination of Remdesivir (REM) in presence of its Alkaline-induced degradation product (AKDP), which is also known to be its metabolite (GS-441524). Recovery rates in plasma were satisfactory at 97.64 ± 1.87, confirming the method's suitability for therapeutic drug monitoring (TDM) in COVID-19 patients. Additionally, the environmental sustainability of the method was evaluated using GAPI, AGREE, and RGB12 metrics, underscoring its green and eco-friendly characteristics."

Journal • Infectious Disease • Novel Coronavirus Disease

Comparative transcriptome analysis of PBMCs in cats diagnosed with and recovered from FIPV. (PubMed, Lab Anim Res) - "This study identified immunological alterations in PBMCs of Normal, FIPD, and FIPR cats. KLF-6 and NF-κB were found to regulate IL-8-mediated neutrophil activation."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CXCL8 • KLF6

Myocarditis in Cats with Feline Infectious Peritonitis Can Be Cured with GS-441524 and Symptomatic Cardiovascular Treatment. (PubMed, Animals (Basel)) - "Myocarditis can be a clinical feature of FIP and present with different cardiologic manifestations. FIP-induced myocarditis can be cured with GS-441524 in combination with symptomatic cardiovascular treatment including pimobendan, clopidogrel, furosemide, or atenolol, depending on the clinical presentation."

Journal • Cardiovascular • Infectious Disease • Inflammation • Novel Coronavirus Disease • TNNI3

Structure elucidation and quantification of the active pharmaceutical ingredient in a non-approved drug and in cat serum using QTRAP-MS/MS and ZenoTOF-MS/MS. (PubMed, J Pharm Biomed Anal) - "The API content was determined to be 21.56 ± 0.98 mg per tablet employing 13C5-GS-441524 as an internal standard to account for potential matrix effects. The API concentration was measured in plasma and serum samples collected at four different time points from six treated cats."

Journal • Infectious Disease • Novel Coronavirus Disease

Prospective Analysis of Clinicopathologic Correlates of At-Home Feline Infectious Peritonitis Treatment Using GS-441524. (PubMed, Pathogens) - "Overall, these data demonstrate a lack of traditional clinicopathologic parameters which are consistently predictive of FIP therapy success. Other predictors of outcome with antiviral therapy should be pursued."

Journal • Infectious Disease • Novel Coronavirus Disease

Porcine Epidemic Diarrhea Virus Is Inhibited by GS-441524 During an In Vitro Infection. (PubMed, Microorganisms) - "Even at a high viral infection dose of MOI 0.5 or added 6 h post-viral infection, 20 μM GS-441524 can still effectively inhibit PEDV proliferation. These findings emphasize the potent antiviral activity of GS-441524 against PEDV, and its therapeutic efficacy on PEDV-infected piglets warrants further investigation."

Journal • Preclinical • Infectious Disease

Rapid Clinical Resolution and Differential Diagnosis of a Neurological Case of Feline Infectious Peritonitis (FIP) Using GS-441524. (PubMed, Pathogens) - "The cat was treated with anticonvulsants (phenobarbital and levetiracetam), an antibiotic (ampicillin/clavulanic acid), and GS-441524. Neurologic signs did not improve on an antibiotic alone but improved significantly after two subcutaneous injections of GS-441524. The cat received an 84-day course of GS-441524 and, at the time of manuscript preparation (over 12 months after diagnosis), remains ambulatory and seizure-free without recurrence of neurologic signs and no detectable viral shedding in feces."

Journal • Ataxia • CNS Disorders • Epilepsy • Hematological Disorders • Infectious Disease • Inflammation • Movement Disorders • Novel Coronavirus Disease

Efficacy of oral remdesivir in treating feline infectious peritonitis: a prospective observational study of 29 cats. (PubMed, J Feline Med Surg) - "Molnupiravir was offered as a rescue therapy for cats that relapsed.ResultsIn total, 25 (86%) cats entered remission and survived beyond 6 months (range 6-27). The survival rate in non-effusive cats was significantly lower; therefore, an increased dose rate or frequency of administration should be considered in these cats. Oral remdesivir is a viable antiviral option where GS-441524 is unavailable."

Journal • Observational data • Infectious Disease • Novel Coronavirus Disease • Ophthalmology

Population Pharmacokinetic Modelling of Remdesivir and Its Metabolite GS-441524 in Hospitalised Patients with COVID-19. (PubMed, Clin Pharmacokinet) - "The licensed remdesivir dose may achieve target concentrations of GS-441524, but higher dosages may optimise outcomes. Dose adjustments are guided primarily by kidney function."

Journal • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

High-dose induction therapy and treatment termination criteria for feline infectious peritonitis with remdesivir, GS-441524 and adjunctive mefloquine: 46 cases (2023). (PubMed, J Small Anim Pract) - "In some cats with feline infectious peritonitis a high-dose induction protocol, using acute-phase proteins and the albumin/globulin ratio for treatment cessation, enabled a shorter treatment period than the conventional 12 weeks, without observed recurrence. The criteria used in this study appear adequate for determining appropriate times for feline infectious peritonitis treatment cessation."

Journal

Treatment of feline infectious peritonitis in cats with molnupiravir: clinical observations and outcomes for 54 cases. (PubMed, Aust Vet J) - "Molnupiravir demonstrated comparable survival outcomes to remdesivir/GS-441524 for treating FIP and serves as an accessible, effective option across various presentations, including ocular and neurologic forms."

Journal • Hematological Disorders • Neutropenia

Feline infectious peritonitis - a current overview (PubMed, Tierarztl Prax Ausg K Kleintiere Heimtiere) - "Studies show that antiviral drugs used in human medicine, such as the nucleoside analog GS-441524, are effective against FIP and can provide affected cats with a survival chance of up to 100%...Furthermore, increasing evidence suggests that FIP is frequently associated with myocarditis. This article provides an overview of the current knowledge on FIP, including its pathology, clinical signs, effective treatment options, and preventive measures."

Journal • Review • Cardiovascular • Infectious Disease • Inflammation • Novel Coronavirus Disease • Vasculitis

REMDESIVIR INDUCED HEART BLOCK - Shazia Pathan (ACC 2025) - "This case presents a life-threatening drug reaction, advocating telemetry monitoring with Remdesivir. The patient being asymptomatic, while in complete A-V dissociation, suggests that this may be more common than we have clinically recognized. The half-life of Remdesivir's active metabolite, GS-441524, is ~27 hours."

Cardiovascular • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Practical approach to development of GS-445124-loaded PLGA nanoparticles for the long-term treatment of feline infectious peritonitis caused by feline coronavirus infection. (PubMed, Int J Pharm) - "When GS-PLGA NP was injected at 22 mg/kg in cats, higher systemic exposure can be expected compared to injecting GS-441524 at 4 mg/kg for one week (relative bioavailability, 152 %). As well as GS-PLGA NP showed lower toxicity, improved cellular uptake, and enhanced antiviral efficacy against FCoV compared to the pure GS-441524."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Pharmacokinetics of GS-441524 following intravenous remdesivir in six cats and results of therapeutic drug monitoring during treatment of feline infectious peritonitis: 22 cases (2021-2024). (PubMed, J Small Anim Pract) - "This study supports the use of RDV and GS-441524 for FIP treatment and suggests that population pharmacokinetic modelling is required to better explore the utility of therapeutic drug monitoring of GS-441524."

Journal • PK/PD data

The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection. (PubMed, Sci Adv) - "Obeldesivir (ODV; GS-5245) is an orally administered ester prodrug of the parent nucleoside GS-441524 that has broad spectrum antiviral activity inhibiting viral RNA-dependent RNA polymerases. For outbreak response, oral antivirals might present substantial advantages over now approved intravenous drugs, such as easy supply, storage, distribution, and administration. Furthermore, these results support the potential of ODV as an oral postexposure prophylaxis with broad spectrum activity across filoviruses."

Journal • Ebola Virus Disease • Infectious Disease • Inflammation

The Nucleoside Analog GS-441524 Effectively Attenuates the In Vitro Replication of Multiple Lineages of Circulating Canine Distemper Viruses Isolated from Wild North American Carnivores. (PubMed, Viruses) - "Six antiviral compounds were selected after preliminary experiments that excluded ribavirin, hesperidin and rutin: a protease inhibitor (nirmatrelvir), a polymerase inhibitor (favipiravir) and four nucleoside analogs (remdesivir, GS-441524, EIDD2801 and EIDD1931). Several of the nucleoside analogs have been safely used previously in carnivore species for the treatment of other viral diseases, suggesting that they may be promising candidates for the treatment of canine distemper in dogs. Our results emphasize the need to consider different viral lineages in the screening of antiviral compounds."

Journal • Preclinical • Infectious Disease

The Combination of GS-441524 (Remdesivir) and Ribavirin Results in a Potent Antiviral Effect Against Human Parainfluenza Virus 3 Infection in Human Airway Epithelial Cell Cultures and in a Mouse Infection Model. (PubMed, Viruses) - "Moreover, several mice in the single-treatment groups exhibited severe lung pathology. These findings may warrant exploring this combination in patients with severe HPIV-3 infections and possibly also against infections with other viruses that are susceptible in vitro to these two drugs."

Journal • Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases

Remdesivir is active in vitro against tick-borne encephalitis virus and selects for resistance mutations in the viral RNA-dependent RNA polymerase. (PubMed, Infect Dis (Lond)) - "TBEV was cultured in A549 cells, and the inhibitory effects of RDV (GS-5734), its parent nucleotide GS-441524, and SOF (GS-7977) were assessed. RDV exhibits potent in vitro antiviral activity against TBEV via specific targeting of the viral RdRp as confirmed by the emergence of resistance-associated double NS5 substitutions in vitro in the presence of RDV. While the potential in vivo implications of the observed RDV resistance remain to be determined, these in vitro data support further assessment of RDV for the treatment of TBEV infection."

Journal • Preclinical • CNS Disorders • Infectious Disease

GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: National Center for Advancing Translational Sciences (NCATS) | N=70 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Infectious Disease • Novel Coronavirus Disease

Pharmacokinetics of SARS-CoV-2 RNA Polymerase Inhibitor Remdesivir in Participants With Moderate and Severe Hepatic Impairment. (PubMed, Clin Transl Sci) - "The prodrug, remdesivir, undergoes metabolic activation inside the cell to form the intracellular active metabolite (GS-443902) along with two plasma metabolites (GS-704277 and GS-441524). Remdesivir was generally safe and well tolerated in hepatically impaired individuals, and the modest exposure increases of remdesivir and its metabolites were not associated with adverse events. Based on these findings, no dose adjustment of remdesivir is recommended for patients with mild, moderate, or severe hepatic impairment."

Clinical • Journal • PK/PD data • Hepatology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Clinical Evaluation of Drug-Drug Interactions with Obeldesivir, an Orally Administered Antiviral Agent. (PubMed, Clin Pharmacol Ther) - "When obeldesivir was tested as a precipitant, pharmacokinetic parameter point estimates for midazolam (CYP3A4 inhibition/induction), caffeine (CYP1A2 inhibition), and metformin (organic cation transporter 1 inhibition) exposures were within 80-125% no-effect bounds representing the interval within which a systemic exposure change does not warrant clinical action based on EMA/FDA guidance. Dabigatran (P-glycoprotein substrate) and pitavastatin (organic anion transporting polypeptide 1B1/1B3 substrate) exposures decreased by approximately 25% and 30%, respectively, with obeldesivir coadministration; these were considered not clinically relevant, as these exposure changes are not associated with dose changes or precautions in the US prescribing information for these drugs. When obeldesivir was evaluated as an object, exposures of GS-441524, the parent nucleoside monophosphate metabolite of obeldesivir, were within the 80-125% no-effect bounds for ritonavir (P-glycoprotein..."

Journal • Breast Cancer • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor • CYP1A2 • SLC22A1

Cepharanthine: A promising natural compound against feline infectious peritonitis virus infection and associated inflammation. (PubMed, Virology) - "The combination of CEP and GS-441524 exhibited synergistic antiviral effects against FIPV infection. Our findings highlight the therapeutic potential of CEP for treatment of FIP."

Journal • Infectious Disease • Inflammation