Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Feline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and in vitro Efficacy of Novel Antivirals in Australian Outbreaks

Matteo Bordicchia
,
Tulio Machado Fumian
ORCID logo ,
Kate Van Brussel
,
Alice G. Russo
,
Maura Carrai
ORCID logo ,
Shi-jia Le
,
Patricia A. Pesavento
,
Edward C. Holmes
ORCID logo ,
Vito Martella
ORCID logo ,
Peter White
ORCID logo ,
Julia A. Beatty
ORCID logo ,
Mang Shi
,
Vanessa R. Barrs
*
Version 1 : Received: 15 August 2021 / Approved: 16 August 2021 / Online: 16 August 2021 (13:50:15 CEST)

A peer-reviewed article of this Preprint also exists.

Bordicchia, M.; Fumian, T.M.; Brussel, K.V.; Russo, A.G.; Carrai, M.; Le, S.-J.; Pesavento, P.A.; Holmes, E.C.; Martella, V.; White, P.; Beatty, J.A.; Shi, M.; Barrs, V.R. Feline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and In Vitro Efficacy of Novel Antivirals in Australian Outbreaks. Viruses 2021, 13, 2040. Bordicchia, M.; Fumian, T.M.; Brussel, K.V.; Russo, A.G.; Carrai, M.; Le, S.-J.; Pesavento, P.A.; Holmes, E.C.; Martella, V.; White, P.; Beatty, J.A.; Shi, M.; Barrs, V.R. Feline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and In Vitro Efficacy of Novel Antivirals in Australian Outbreaks. Viruses 2021, 13, 2040.

Abstract

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2’-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino acid residues from the hypervariable E region of the capsid in the cultured viruses provided no support for the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4-0.6 µM, TI 21; 2CMC EC50, 2.7-5.3 µM, TI >18; NITD-008, 0.5 to 0.9 µM, TI >111. Investigation of these antivirals for treatment of FCV-VSD is warranted.

Keywords

Caliciviridae; Vesivirus; Nitazoxanide; 2’-C-methylcytidine; NITD-008; cats

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (1)

Comment 1
Received: 22 August 2021
Commenter:
Richard Malik

The commenter has declared there is no conflict of interests.
Comment: The Abstract says:
The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV have yet to be developed.

But there is good work from the same University as the authors that mefloquine has good efficacy against Calicivirus, and these studies have progressed to pharmacokinetic studies in cats. Amazing not to cite this work!?

McDonagh P, Sheehy PA, Fawcett A, Norris JM. Antiviral effect of mefloquine on feline calicivirus in vitro. Vet Microbiol. 2015 Apr 17;176(3-4):370-7. doi: 10.1016/j.vetmic.2015.02.007. Epub 2015 Feb 16. PMID: 25746684; PMCID: PMC7127475.

Pharmacokinetic Profile of Oral Administration of Mefloquine to Clinically Normal Cats: A Preliminary In-Vivo Study of a Potential Treatment for Feline Infectious Peritonitis (FIP).
Yu J, Kimble B, Norris JM, Govendir M.
Animals (Basel). 2020 Jun 8;10(6):1000. doi: 10.3390/ani10061000.
PMID: 32521771
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