Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524

As previously demonstrated by our research group, the oral multicomponent drug Xraphconn<sup>®</sup> containing GS-441524 was effective at curing otherwise fatal feline infectious peritonitis (FIP) in 18 feline coronavirus (FCoV)-infected cats. The aims of the current study were to inves...

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Main Authors: Marina L. Meli, Andrea M. Spiri, Katharina Zwicklbauer, Daniela Krentz, Sandra Felten, Michèle Bergmann, Roswitha Dorsch, Kaspar Matiasek, Martin Alberer, Laura Kolberg, Ulrich von Both, Katrin Hartmann, Regina Hofmann-Lehmann
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Language:English
Published: MDPI AG 2022-05-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/14/5/1069
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author Marina L. Meli
Andrea M. Spiri
Katharina Zwicklbauer
Daniela Krentz
Sandra Felten
Michèle Bergmann
Roswitha Dorsch
Kaspar Matiasek
Martin Alberer
Laura Kolberg
Ulrich von Both
Katrin Hartmann
Regina Hofmann-Lehmann
author_facet Marina L. Meli
Andrea M. Spiri
Katharina Zwicklbauer
Daniela Krentz
Sandra Felten
Michèle Bergmann
Roswitha Dorsch
Kaspar Matiasek
Martin Alberer
Laura Kolberg
Ulrich von Both
Katrin Hartmann
Regina Hofmann-Lehmann
author_sort Marina L. Meli
collection DOAJ
description As previously demonstrated by our research group, the oral multicomponent drug Xraphconn<sup>®</sup> containing GS-441524 was effective at curing otherwise fatal feline infectious peritonitis (FIP) in 18 feline coronavirus (FCoV)-infected cats. The aims of the current study were to investigate, using samples from the same animals as in the previous study, (1) the effect of treatment on fecal viral RNA shedding; (2) the presence of spike gene mutations in different body compartments of these cats; and (3) viral RNA shedding, presence of spike gene mutations, and anti-FCoV antibody titers in samples of 12 companion cats cohabitating with the treated cats. Eleven of the eighteen treated FIP cats (61%) were shedding FCoV RNA in feces within the first three days after treatment initiation, but all of them tested negative by day 6. In one of these cats, fecal shedding reoccurred on day 83. Two cats initially negative in feces were transiently positive 1–4 weeks into the study. The remaining five cats never shed FCoV. Viral RNA loads in feces decreased with time comparable with those in blood and effusion. Specific spike gene mutations linked to systemic FCoV spread were consistently found in blood and effusion from treated FIP cats, but not in feces from treated or companion cats. A new mutation that led to a not yet described amino acid change was identified, indicating that further mutations may be involved in the development of FIP. Eight of the twelve companion cats shed FCoV in feces. All but one of the twelve companion cats had anti-FCoV antibodies. Oral treatment with GS-441524 effectively decreased viral RNA loads in feces, blood, and effusion in cats with FIP. Nonetheless, re-shedding can most likely occur if cats are re-exposed to FCoV by their companion cats.
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spelling doaj.art-b3719879ab3041c393a2d3d8b128de982023-11-23T13:32:51ZengMDPI AGViruses1999-49152022-05-01145106910.3390/v14051069Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524Marina L. Meli0Andrea M. Spiri1Katharina Zwicklbauer2Daniela Krentz3Sandra Felten4Michèle Bergmann5Roswitha Dorsch6Kaspar Matiasek7Martin Alberer8Laura Kolberg9Ulrich von Both10Katrin Hartmann11Regina Hofmann-Lehmann12Clinical Laboratory, Department of Clinical Diagnostics and Services, Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, SwitzerlandClinical Laboratory, Department of Clinical Diagnostics and Services, Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, SwitzerlandClinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, D-80539 Munich, GermanyClinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, D-80539 Munich, GermanyClinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, D-80539 Munich, GermanyClinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, D-80539 Munich, GermanyClinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, D-80539 Munich, GermanySection of Clinical & Comparative Neuropathology, Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, LMU Munich, D-80539 Munich, GermanyDivision of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, LMU-Munich, D-80337 Munich, GermanyDivision of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, LMU-Munich, D-80337 Munich, GermanyDivision of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, LMU-Munich, D-80337 Munich, GermanyClinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, D-80539 Munich, GermanyClinical Laboratory, Department of Clinical Diagnostics and Services, Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, CH-8057 Zurich, SwitzerlandAs previously demonstrated by our research group, the oral multicomponent drug Xraphconn<sup>®</sup> containing GS-441524 was effective at curing otherwise fatal feline infectious peritonitis (FIP) in 18 feline coronavirus (FCoV)-infected cats. The aims of the current study were to investigate, using samples from the same animals as in the previous study, (1) the effect of treatment on fecal viral RNA shedding; (2) the presence of spike gene mutations in different body compartments of these cats; and (3) viral RNA shedding, presence of spike gene mutations, and anti-FCoV antibody titers in samples of 12 companion cats cohabitating with the treated cats. Eleven of the eighteen treated FIP cats (61%) were shedding FCoV RNA in feces within the first three days after treatment initiation, but all of them tested negative by day 6. In one of these cats, fecal shedding reoccurred on day 83. Two cats initially negative in feces were transiently positive 1–4 weeks into the study. The remaining five cats never shed FCoV. Viral RNA loads in feces decreased with time comparable with those in blood and effusion. Specific spike gene mutations linked to systemic FCoV spread were consistently found in blood and effusion from treated FIP cats, but not in feces from treated or companion cats. A new mutation that led to a not yet described amino acid change was identified, indicating that further mutations may be involved in the development of FIP. Eight of the twelve companion cats shed FCoV in feces. All but one of the twelve companion cats had anti-FCoV antibodies. Oral treatment with GS-441524 effectively decreased viral RNA loads in feces, blood, and effusion in cats with FIP. Nonetheless, re-shedding can most likely occur if cats are re-exposed to FCoV by their companion cats.https://www.mdpi.com/1999-4915/14/5/1069FIPFCoVsheddingviral loadsspike gene mutationstherapy
spellingShingle Marina L. Meli
Andrea M. Spiri
Katharina Zwicklbauer
Daniela Krentz
Sandra Felten
Michèle Bergmann
Roswitha Dorsch
Kaspar Matiasek
Martin Alberer
Laura Kolberg
Ulrich von Both
Katrin Hartmann
Regina Hofmann-Lehmann
Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524
Viruses
FIP
FCoV
shedding
viral loads
spike gene mutations
therapy
title Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524
title_full Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524
title_fullStr Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524
title_full_unstemmed Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524
title_short Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524
title_sort fecal feline coronavirus rna shedding and spike gene mutations in cats with feline infectious peritonitis treated with gs 441524
topic FIP
FCoV
shedding
viral loads
spike gene mutations
therapy
url https://www.mdpi.com/1999-4915/14/5/1069
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