Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials

Viruses, Год журнала: 2024, Номер 16(3), С. 462 - 462

Опубликована: Март 17, 2024

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with genetic variant feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at University California, Davis. Collectively, total 60 client-owned cats, each confirmed diagnosis naturally occurring FIP, were treated variety compounds. The tested therapies included compounds GS-441524, remdesivir, molnupiravir and allogeneic mesenchymal stem/stroma cell transfusions. Four did not meet inclusion criteria for therapies; these in set untreated control cats. ELISA Western blot assays using serum/plasma or ascites effusions obtained subset Normalized tissue/effusion viral loads determined 34 quantitative RT-PCR nucleic acids isolated either abdominal lymph node tissue. Twenty-one PCR “serotyped” (genotyped) had S1/S2 region coronaviral spike gene amplified, cloned sequenced In total, 3 14 (23.3%) antiviral-treated died euthanized during (13) after completion (1) treatment. Of 17 13 complete necropsies (10 antivirals cats). found that anticoronaviral serologic responses persistent robust throughout treatment period, primarily IgG isotype, focused on structural Nucleocapsid Membrane proteins. Coronavirus patterns similar entering remission died. Viral RNA was readily detectable majority tissue effusions, all isolates be serotype I FIPV. became undetectable 11 days post-treatment sensitive assay. most common pathologic lesions identified necropsied hepatitis, effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus perivasculitis. compounds, gross histological characteristic persisted several weeks, while antigen progressively less detectable.

Язык: Английский

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In Vitro Evaluation of Aryl Hydrocarbon Receptor Involvement in Feline Coronavirus Infection

Viruses, Год журнала: 2025, Номер 17(2), С. 227 - 227

Опубликована: Фев. 6, 2025

Feline coronavirus (FCoV) is an alphacoronavirus (αCoV) that causes moderate or chronic asymptomatic infection in cats. However, a single infected cat, FCoV can modify its cellular tropism by acquiring the ability to infect macrophages, resulting development of feline infectious peritonitis (FIP). In this context, restrain impact infection, scientific research has focused attention on antiviral therapies involving novel mechanisms action. Recent studies have demonstrated aryl hydrocarbon receptor (AhR) signaling regulates host response different human and animal CoVs. Hence, mechanism action AhR was evaluated upon Crandell Kidney (CRFK) canine fibrosarcoma (A72) cells. Following with enteric CoV (FECV), strain "München", significant activation target CYP1A1, observed. The selective antagonist CH223191 provoked reduction replication levels viral nucleocapsid protein (NP). Furthermore, effect inhibitor acidity lysosomes cells Our findings indicate acts upregulates AhR. repressed virus yield through inhibition respect, for counteracting FCoV, represents new useful identifying drugs. Moreover, presence CH223191, alkalinization FCoV-infected CRFK detected, outlining their involvement activity.

Язык: Английский

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Molnupiravir treatment of 18 cats with feline infectious peritonitis: A case series

Journal of Veterinary Internal Medicine, Год журнала: 2023, Номер 37(5), С. 1876 - 1880

Опубликована: Авг. 8, 2023

Abstract Background Feline infectious peritonitis (FIP) is a viral disease in cats, caused by certain strains of coronavirus and has high case fatality rate. Objective This series reports the outcomes treatment cats with FIP using molnupiravir. Animals Eighteen diagnosed at You‐Me Animal Clinic, Sakura‐shi, Japan between January August 2022, whose owners gave informed consent to this experimental treatment. Methods For prospective observational study, molnupiravir tablets were compounded in‐house Clinic. Owners administered 10‐20 mg/kg PO twice daily. Standard duration was 84 days. Results Among 18 13 had effusive 5 noneffusive FIP. Three neurological or ocular signs before Four all FIP, died euthanized within 7 days starting The remaining 14 completed remained remission time writing (139‐206 after treatment). Elevated serum alanine transaminase (ALT) activity found 3 Days 7‐9, recovered without management. Two jaundice hospitalized, 1 during (Day 37) severe anemia start Conclusions Clinical Importance suggests that might be an effective safe for domestic dose

Язык: Английский

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Die feline infektiöse Peritonitis – ein aktueller Überblick

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere, Год журнала: 2025, Номер 53(02), С. 96 - 102

Опубликована: Апрель 1, 2025

Zusammenfassung Coronaviren (CoVs) sind positiv einzelsträngige RNA-Viren, die verschiedene Tierarten sowie Menschen infizieren können. Besonders relevant für Katzen ist das feline Coronavirus (FCoV), in Katzenpopulationen weltweit verbreitet ist. Eine Infektion mit FCoV verläuft der Regel ohne Symptome. In Mehrkatzenhaushalten entwickeln jedoch etwa 5–12% FCoV-infizierten aufgrund von Mutationen im Spike-Gen infektiöse Peritonitis (FIP). FIP eine immunvermittelte Erkrankung, bislang immer tödlich verlief. Die führen zu einem Tropismus-Wechsel Enterozyten Monozyten und Makrophagen. Der damit verbundene Wechsel Virulenz führt charakteristischen granulomatösen Vaskulitis Perivaskulitis, bei beobachtet wird. letzter Zeit gibt es zahlreiche neue Erkenntnisse zur FIP. So zeigen Studien, dass humanmedizinische antivirale Medikamente, wie Nukleosidanalogon GS-441524, wirksam betroffenen Überlebenschance bis 100% bieten. Zudem wurde neuartige FCoV-Variante, FCoV-23, aus Zypern identifiziert. Dieses Virus entstand nach derzeitigem Kenntnisstand durch Rekombination zwischen dem hochvirulenten pantropischen caninen Coronavirus; kann direkt Katze übertragen werden auslösen. Darüber hinaus mehr Hinweise darauf, häufig einer Myokarditis assoziiert Dieser Artikel bietet einen Überblick über den aktuellen Wissensstand FIP, unter Berücksichtigung Pathologie, klinischer Symptome, wirksamer Therapiemöglichkeiten Präventionsmaßnahmen.

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Treatment of feline infectious peritonitis in cats with molnupiravir: clinical observations and outcomes for 54 cases

Australian Veterinary Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 15, 2025

Objective To evaluate the clinical applications and treatment outcomes using molnupiravir for of naturally occurring feline infectious peritonitis virus (FIPv). Methods Ninety‐two client‐owned cats with confirmed or presumptive FIP were retrospectively recruited from 35 veterinary practices, primarily in Australia, between February 2023 March 2024. Cats categorised based on received: Cohort A: Molnupiravir treatment: monotherapy, maintenance rescue therapy; B: Remdesivir and/or GS‐441524 treatment. Seventy‐eight enrolled. was administered orally a median 84 days, at dose 13.3 mg/kg BID. Remission defined as resolution FIP‐related signs (i) normalisation serum globulin concentrations A:G ratio (≥0.6), (ii) sustained remission least 100 days after stopping anti‐viral therapy. Cure rate percentage achieving remission, without requiring therapy experiencing relapsed disease. Results monotherapy resulted cure 72% (13/18) while achieved 86% (25/29), utilised 100% (7/7). Treatment remdesivir/GS‐441524 71% (17/24 cats). Survival analysis revealed no difference treated those remdesivir/GS‐441524. Adverse events associated included neutropenia, transient elevations hepatic enzymes. Conclusion demonstrated comparable survival to treating serves an accessible, effective option across various presentations, including ocular neurologic forms.

Язык: Английский

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Effect of Nucleic Acid Analog Administration on Fluctuations of Albumin to Globulin Ratio in Cats with Feline Infectious Peritonitis

Опубликована: Март 12, 2024

Background: Feline infectious peritonitis (FIP) is a fatal feline disease classified as either effusive (‘wet’), non-effusive (‘dry’), or mixture of both forms (‘mixed’). The anti-FIP therapeutic effect Mutian and molnupiravir, two drugs whose active ingredient nucleic acid analog, has been confirmed recently. Methods: Of the cats with FIP, we observed total 122 56 cases achieved remission after administration molnupiravir routine treatments, respectively. Changes in clinical indicators suggested to be correlated FIP (weight, hematocrit, albumin globulin ratio) before each drug during follow-up observation were statistically compared for type. Results: In all three types, resulted significant increases these indicators. Furthermore, on improving ratio was not at wet that but mixed dry (P<0.02 P<0.003, respectively). These features due differences fluctuations circulating levels. Conclusions: results indicate slight inflammatory responses might elicited continuously by residual coronavirus non-disappeared through treatments.

Язык: Английский

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Open label clinical trial of orally administered molnupiravir as a first‐line treatment for naturally occurring effusive feline infectious peritonitis

Journal of Veterinary Internal Medicine, Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

Abstract Background Before the discovery of effective antiviral drugs, feline infectious peritonitis (FIP) was a uniformly fatal disease cats. Multiple treatments have been recognized, but optimization treatment protocols is needed. Objective To evaluate efficacy PO molnupiravir (MPV; EIDD‐2801) to treat effusive FIP. Animals Ten cats with naturally occurring FIP and 10 historical control treated GS‐441524. Methods A single‐center, prospective, open‐label longitudinal, non‐inferiority trial controls. were enrolled MPV (10‐15 mg/kg q12h) for 84 days. Cats evaluated at 0, 6, 16 weeks, proportion in clinical remission weeks determined. Survival clinicopathologic features compared Results Eight survived weeks. The 2 non‐survivors died first 24 hours treatment. No adverse events that necessitated discontinuation observed. non‐inferior historic GS‐441524 (5/9 [55%] survived), difference survival 25% (90% confidence interval, −9.3% 59.3%). Clinicopathologic associated normalized during study period, no differences data each time point observed when comparing Conclusions Clinical Importance Molnupiravir an

Язык: Английский

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Effect of Nucleic Acid Analog Administration on Fluctuations in the Albumin-to-Globulin Ratio in Cats with Feline Infectious Peritonitis

Animals, Год журнала: 2024, Номер 14(9), С. 1322 - 1322

Опубликована: Апрель 28, 2024

Background: feline infectious peritonitis (FIP) is a fatal disease in cats classified as either effusive (‘wet’), non-effusive (‘dry’), or mixture of both forms (‘mixed’). The anti-FIP therapeutic effects Mutian and molnupiravir, two drugs with nucleic acid analog an active ingredient, have been confirmed recently. Methods: Of the FIP, we observed total 122 56 cases that achieved remission after administration molnupiravir routine treatments, respectively. Changes clinical indicators suggested to be correlated FIP (weight, hematocrit, albumin-to-globulin ratio) before each drug during follow-up observation were statistically compared for type. Results: In all three types, resulted significant increases these indicators. Furthermore, effect on improving ratio was not at wet but mixed dry (p < 0.02 p 0.003, respectively). differences due those circulating globulin levels. Conclusions: These results indicate slight inflammatory responses might elicited continuously by residual virus persisted through treatments.

Язык: Английский

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GS-441524 and molnupiravir are similarly effective for the treatment of cats with feline infectious peritonitis

Frontiers in Veterinary Science, Год журнала: 2024, Номер 11

Опубликована: Июль 18, 2024

Although not registered for feline infectious peritonitis (FIP) in Japan, nucleoside analogs have shown efficacy and we been offering them to owners of cats with FIP at our clinic since January 2020. The aim this study was investigate outcomes who received GS-441524 or molnupiravir. Diagnosis based on clinical signs, laboratory test results, the presence coronavirus RNA blood effusion aspirate. After providing verbal written information, a presumptive diagnosis were offered antiviral treatment commercially sourced from June 2020, either compounded molnupiravir 2022. Dosing 12.5–25 mg/kg/day 20–40 molnupiravir, depending neurological and/or ocular continued 84 days. Overall, 118 (effusive 76) treatment, 59 GS-4421524 Twenty died, 12/59 (20.3%) group 8/59 (13.6%) ( p = 0.326), most deaths within first 10 days starting treatment. Among survivors, signs resolved all but one cat, had persistent seizures. Of completing 48/48 51/52 achieved remission. Laboratory parameters normalized 6 7 weeks drug administration. Adverse events, such as primarily hepatic function abnormalities, transient without specific intervention. Our data indicate that show similar effects safety FIP.

Язык: Английский

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Rethinking the Drivers of Coronavirus Virulence and Pathogenesis: Toward an Understanding of the Dynamic World of Mutations, Indels, and Recombination Within the Species Alphacoronavirus-1

Опубликована: Ноя. 26, 2024

Alphacoronaviruses are widespread but understudied in comparison to betacoronaviruses. Recombination, mutations, and indels hallmarks of coronavirus replication, which together facilitate viral spillover emergence, especially within the alphacoronaviruses. The species _Alphacoronavirus-1_ comprises distinct viruses cats, dogs pigs. In high-pathogenicity feline (FCoV) is infamous as cause infectious peritonitis (FIP), a lethal disease that can now be treated with antiviral drugs. FCoV-1 exists two genotypes (type -1 -2) transmitted low-pathogenicity virus causes mild or asymptomatic disease. FCoV variants arise cats already infected FCoV, while mutations responsible for this phenotype change remain enigmatic, main determinant pathogenicity spike glycoprotein. outcome driven by combination both within- between-host evolution, whereas FCoV-2 appears recombination co-circulating canine coronaviruses (CCoV). virulence largely explained using “furin cleavage site (FCS) disruption hypothesis,” argues contains an intact FCS has disrupted unable cleaved. pathogenesis exemplified FCoV-23, novel canine/feline recombinant caused outbreak severe Cyprus during 2023. As such, _Alphacoronavirus-1 _mayexist adynamic "metavirome"1 constant state flux, presenting notable challenges surveillance management, risk-assessment.

Язык: Английский

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