Dataset Information

Potential Therapeutic Agents for Feline Calicivirus Infection.

ABSTRACT: Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV protease-polymerase protein, we established two in vitro assays to assess the inhibitory activity of compounds directly against the FCV protease or polymerase. Using this recombinant enzyme, we identified quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC50 values of 2.8 ?M and 2.7 ?M, respectively). We also demonstrate the inhibition of FCV protease activity by GC376 (IC50 of 18 µM). Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2'-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC50 values in the low micromolar range (0.6 ?M and 2.5 ?M, respectively). In conclusion, we established two in vitro assays that will accelerate the research for FCV antivirals and can be used for the high-throughput screening of direct-acting antivirals.

SUBMITTER: Fumian TM

PROVIDER: S-EPMC6116245 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Potential Therapeutic Agents for Feline Calicivirus Infection.

Fumian Tulio M TM Tuipulotu Daniel Enosi DE Netzler Natalie E NE Lun Jennifer H JH Russo Alice G AG Yan Grace J H GJH White Peter A PA

Viruses 20180816 8

Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV pr ...[more]

PMID: 30115859

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Project description:Bayesian network (BN) modeling is a rich and flexible analytical framework capable of elucidating complex veterinary epidemiological data. It is a graphical modeling technique that enables the visual presentation of multi-dimensional results while retaining statistical rigor in population-level inference. Using previously published case study data about feline calicivirus (FCV) and other respiratory pathogens in cats in Switzerland, a full BN modeling analysis is presented. The analysis shows that reducing the group size and vaccinating animals are the two actionable factors directly associated with FCV status and are primary targets to control FCV infection. The presence of gingivostomatitis and Mycoplasma felis is also associated with FCV status, but signs of upper respiratory tract disease (URTD) are not. FCV data is particularly well-suited to a network modeling approach, as both multiple pathogens and multiple clinical signs per pathogen are involved, along with multiple potentially interrelated risk factors. BN modeling is a holistic approach-all variables of interest may be mutually interdependent-which may help to address issues, such as confounding and collinear factors, as well as to disentangle directly vs. indirectly related variables. We introduce the BN methodology as an alternative to the classical uni- and multivariable regression approaches commonly used for risk factor analyses. We advise and guide researchers about how to use BNs as an exploratory data tool and demonstrate the limitations and practical issues. We present a step-by-step case study using FCV data along with all code necessary to reproduce our analyses in the open-source R environment. We compare and contrast the findings of the current case study using BN modeling with previous results that used classical regression techniques, and we highlight new potential insights. Finally, we discuss advanced methods, such as Bayesian model averaging, a common way of accounting for model uncertainty in a Bayesian network context.

Dataset Information

Potential Therapeutic Agents for Feline Calicivirus Infection.

Publications

Potential Therapeutic Agents for Feline Calicivirus Infection.

Similar Datasets

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