GS-441524 / Copycat Sci - LARVOL DELTA

Whole blood RNA profiling in cats dissects the host immunological response during recovery from feline infectious peritonitis. (PubMed, PLoS One) - "Our research group recently demonstrated successful treatment of cats with naturally occurring FIP using the antiviral nucleoside analogue GS-441524...The results of the present study suggest that elimination of the virus from the blood leads to rapid control and subsequent normalization of the damaging immune response, a finding that corresponds well to the clinical response to treatment. This study illustrates the host response to treatment at the molecular level and provides further evidence that a shorter treatment duration than the 84 days predominantly practiced is sufficient."

Journal • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

Development of GFP-expressing infectious clones for PRRSV using TAR cloning for antiviral drug screening. (PubMed, Npj Viruses) - "Screening SARS-CoV-2 antivirals showed potent inhibition by the multitarget drug ribavirin, the polymerase inhibitors remdesivir and its metabolite GS-441524. Molnupiravir, targeting the polymerase by a different mechanism, showed reduced efficacy against PRRSV, while the protease inhibitor GC376 was ineffective...In contrast, structural divergence in proteases correlated with GC376's inefficacy. These findings underscore the utility of the TAR cloning for arterivirus engineering, with potential applications in vector vaccine development."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Obeldesivir and GS-441524 Antiviral Activity against L Protein Mutants in Respiratory Syncytial Virus (RSV) Minigenome and Recombinant Infectious Virus Systems (IDWeek 2025) - No abstract available

Infectious Disease • Respiratory Syncytial Virus Infections

GS-441524 Treatment in a Cat With Feline Infectious Peritonitis Virus and Pyogranulomatous Transverse Colon Lesion. (PubMed, In Vivo) - "This case report describes a rare presentation of FIP virus infection, characterized by localized lesions confined to a specific segment of the colon. In this case, treatment with the nucleoside analog GS-441524 was very effective in improving the localized lesion and demonstrated excellent efficacy in clearing the FIP virus."

Journal • Anorexia • Colorectal Cancer • Gastrointestinal Disorder • Hodgkin Lymphoma • Infectious Disease • Inflammation • Novel Coronavirus Disease

Antiviral and Immunomodulatory Effects of α-Mangostin Against Feline Infectious Peritonitis Virus: In Vitro Assay. (PubMed, Animals (Basel)) - "Drug combination studies using the ZIP model revealed enhanced cooperative effects when AMEs and α-MG were combined with GC-376 or GS-441524, with GC-376 combinations showing particularly strong synergistic potential. These findings suggest that α-MG and AMEs are promising candidates for FIPV treatment, either as monotherapy or in combination therapy. This study provides insights into developing novel therapeutic strategies to combat FIPV infections and offers a foundation for future veterinary antiviral drug development."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • IFNB1 • IL6 • TNFA

A dual-strategy approach to improve GS-441524 therapy in feline infectious peritonitis: salt engineering and orally disintegrating tablet development. (PubMed, Int J Pharm) - "The GS-S-based ODT (GS-S ODT) maintained pharmacokinetic properties comparable to GS-S powder, confirming its potential as a practical alternative. This study explores advancements in GS formulation by integrating enhanced bioavailability with improved administration convenience, providing a foundation for more effective and accessible FIP treatments to address key challenges in feline healthcare."

Journal • Infectious Disease • Novel Coronavirus Disease

Identification of potential inhibitors of the main protease from feline infectious peritonitis virus using molecular docking and dynamic simulation approaches. (PubMed, PeerJ) - "Our results show that out of the 15 antiviral and immunomodulatory compounds, the top-ranked inhibitors for the FIPV-Mpro are reference standard inhibitor (N3), Sofosbuvir, and the GS-441524, out of which GS-441524 was suggested as Mpro-inhibitor on the basis of further investigation through molecular dynamics simulation method. Further in vitro and in vivo studies are encouraged to test the efficacy of these identified compounds as potent inhibitors for the Mpro of the FIPV in cats. This study will pave the way for the development of novel drugs that treat FIPV infection in cats."

Journal • Infectious Disease • Novel Coronavirus Disease

Dynamic shifts in gut microbiota composition of cats following oral infection with the virulent FIPV strain rQS-79 and treatment with GS-441524. (PubMed, Vet Microbiol) - "These findings highlight that both viral infection and antiviral treatment disrupt the gut microbial balance. Thus, an integrated approach combining antiviral drugs, probiotics, and dietary modulation may offer a more effective strategy for restoring microbiota homeostasis and improving the outcomes of FIP and similar viral infections in cats."

Journal • Infectious Disease • Novel Coronavirus Disease

Repurposing of Some Nucleoside Analogs Targeting Some Key Proteins of the Avian H5N1 Clade 2.3.4.4b to Combat the Circulating HPAI in Birds: An In Silico Approach. (PubMed, Viruses) - "(3) Molecular docking revealed strong binding affinities for both sofosbuvir and GS441524, particularly with the NA and PB2/CBD protein targets...The MM-GBSA binding free energy calculations further supported these findings, as GS441524 displayed more favorable binding energies compared to several known standard inhibitors, including F0045S for HA, Zanamivir for NA, Rimantadine and Amantadine for M2, and PB2-39 for PB2/CBD...These results further support the potential repurposing of GS441524 as a promising therapeutic candidate against H5N1 avian influenza clade 2.3.4.4b. However, further functional studies are required to validate these in silico predictions and support the inhibitory action of GS441524 against the targeted proteins of H5N1, specifically clade 2.3.4.4b."

Journal • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Efficacy of GS-441524 for Feline Infectious Peritonitis: A Systematic Review (2018-2024). (PubMed, Pathogens) - "In summary, this synthesis indicates that GS-441524 is a highly promising treatment for FIP, with a high success rate among treated cases. Nevertheless, randomized controlled trials are needed to establish evidence-based therapeutic protocols tailored to different FIP presentations."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

A Novel HPLC-MS/MS Method for the Intracellular Quantification of the Active Triphosphate Metabolite of Remdesivir: GS-443902. (PubMed, J Xenobiot) - "This work represents the first method for the direct quantification of GS-443902 in PBMCs, with possible future application to intracellular pharmacokinetic studies in different scenarios, such as new oral prodrugs or drug-drug interaction studies."

Journal • Infectious Disease • Novel Coronavirus Disease

Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys. (PubMed, Nat Commun) - "Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase...In an African green monkey RSV infection model, once-daily oral ODV doses of 30 or 90 mg/kg initiated ~24 hours post-infection significantly reduces log10 viral RNA copies/mL × day area under the curve by 69-92% in the upper and lower respiratory tracts. Together, these preclinical data support the clinical evaluation of ODV for the treatment of RSV infection."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

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