Cargando…

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(®) 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...

Descripción completa

Detalles Bibliográficos
Autores principales: Meli, Marina L., Spiri, Andrea M., Zwicklbauer, Katharina, Krentz, Daniela, Felten, Sandra, Bergmann, Michèle, Dorsch, Roswitha, Matiasek, Kaspar, Alberer, Martin, Kolberg, Laura, von Both, Ulrich, Hartmann, Katrin, Hofmann-Lehmann, Regina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147249/
https://www.ncbi.nlm.nih.gov/pubmed/35632813
http://dx.doi.org/10.3390/v14051069
_version_ 1784716761547931648
author Meli, Marina L.
Spiri, Andrea M.
Zwicklbauer, Katharina
Krentz, Daniela
Felten, Sandra
Bergmann, Michèle
Dorsch, Roswitha
Matiasek, Kaspar
Alberer, Martin
Kolberg, Laura
von Both, Ulrich
Hartmann, Katrin
Hofmann-Lehmann, Regina
author_facet Meli, Marina L.
Spiri, Andrea M.
Zwicklbauer, Katharina
Krentz, Daniela
Felten, Sandra
Bergmann, Michèle
Dorsch, Roswitha
Matiasek, Kaspar
Alberer, Martin
Kolberg, Laura
von Both, Ulrich
Hartmann, Katrin
Hofmann-Lehmann, Regina
author_sort Meli, Marina L.
collection PubMed
description As previously demonstrated by our research group, the oral multicomponent drug Xraphconn(®) 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.
format Online
Article
Text
id pubmed-9147249
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91472492022-05-29 Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524 Meli, Marina L. Spiri, Andrea M. Zwicklbauer, Katharina Krentz, Daniela Felten, Sandra Bergmann, Michèle Dorsch, Roswitha Matiasek, Kaspar Alberer, Martin Kolberg, Laura von Both, Ulrich Hartmann, Katrin Hofmann-Lehmann, Regina Viruses Article As previously demonstrated by our research group, the oral multicomponent drug Xraphconn(®) 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. MDPI 2022-05-17 /pmc/articles/PMC9147249/ /pubmed/35632813 http://dx.doi.org/10.3390/v14051069 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Meli, Marina L.
Spiri, Andrea M.
Zwicklbauer, Katharina
Krentz, Daniela
Felten, Sandra
Bergmann, Michèle
Dorsch, Roswitha
Matiasek, Kaspar
Alberer, Martin
Kolberg, Laura
von Both, Ulrich
Hartmann, Katrin
Hofmann-Lehmann, Regina
Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147249/
https://www.ncbi.nlm.nih.gov/pubmed/35632813
http://dx.doi.org/10.3390/v14051069
work_keys_str_mv AT melimarinal fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT spiriandream fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT zwicklbauerkatharina fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT krentzdaniela fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT feltensandra fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT bergmannmichele fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT dorschroswitha fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT matiasekkaspar fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT alberermartin fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT kolberglaura fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT vonbothulrich fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT hartmannkatrin fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524
AT hofmannlehmannregina fecalfelinecoronavirusrnasheddingandspikegenemutationsincatswithfelineinfectiousperitonitistreatedwithgs441524