Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus

Barua, Subarna; Kaltenboeck, Bernhard; Juan, Yen-Chen; Bird, Richard M.; Wang, Chengming

doi:10.3390/vetsci10080513

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…As we observed no severe damage in HAEs infected with SARS-CoV-2, we could confirm that ruxolitinib effectively inhibited the ISG expression. Although we did not evaluate the cytotoxic concentrations of both inhibitors in HAEs, concentrations of at least 5 µM of ruxolitinib and 6 µM of BX795 were not shown to cause any cytotoxicity in various cell lines, including human airway cells [51][52][53][54][55][56]. For instance, nasal HAEs have been exposed to 10 µM of ruxolitinib [50] and 6 µM of BX795 [4,22,23] without any cytotoxicity being noted.…”

Section: Discussionmentioning

confidence: 99%

Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses

Gilbert-Girard,

Piret,

Carbonneau

et al. 2024

Preprint

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Some respiratory viruses can cause a viral interference through the activation of the interferon (IFN) pathway that reduces the replication of another virus. Epidemiological studies of coinfections between SARS-CoV-2 and other respiratory viruses have been hampered by non-pharmaceutical measures applied to mitigate the spread of SARS-CoV-2 during the COVID-19 pandemic. With the ease of these interventions, SARS-CoV-2 and influenza A viruses can now co-circulate. It is thus of prime importance to characterize their interactions. In this work, we investigated viral interference effects between an Omicron variant and a contemporary influenza A/H3N2 strain, in comparison with an ancestral SARS-CoV-2 strain and the 2009 pandemic influenza A/H1N1 virus. We infected nasal human airway epitheliums with SARS-CoV-2 and influenza, either simultaneously or 24 h apart. Viral load was measured by RT-qPCR and IFN-α/β/λ1/λ2 proteins were quantified by immunoassay. Expression of four interferon-stimulated genes (ISGs; OAS1/IFITM3/ISG15/MxA) was also measured by RT-droplet digital PCR. Additionally, susceptibility of each virus to IFN-α/β/λ2 recombinant proteins was determined. Our results showed that influenza A, and especially A/H3N2, interfered with both SARS-CoV-2 viruses, but that SARS-CoV-2 only interfered with A/H1N1. Consistently with these results, influenza, and particularly the A/H3N2 strain, caused a higher production of IFN proteins and expression of ISGs than SARS-CoV-2. The IFN production induced by SARS-CoV-2 was marginal and its presence during coinfections with influenza was associated with a reduced IFN response. All viruses were susceptible to exogenous IFNs, with the ancestral SARS-CoV-2 and Omicron being less susceptible to type I and type III IFNs, respectively. Thus, influenza A causes a viral interference towards SARS-CoV-2 most likely through an IFN response. The opposite is not necessarily true, and a concurrent infection with both viruses leads to a lower IFN response. Taken together, these results help us to understand how SARS-CoV-2 interacts with another major respiratory pathogen.

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Section: Discussionmentioning

confidence: 99%

Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses

Gilbert-Girard,

Piret,

Carbonneau

et al. 2024

Preprint

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“…Antiviral drugs like GS-441524 and remdesivir have been investigated for their efficacy against FIPV, and GS-441524 has shown promising results in reducing viral replication (Barua et al, 2023). This highlights the potential for reevaluating current antiviral agents for FIPV management.…”

Section: Introductionmentioning

confidence: 99%

Theoretical studies of phytochemicals with feline infectious peritonitis virus proteins: a search for novel antivirals

Kurt

2024

International Journal of Agriculture Environment and Food Sciences

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Feline Infectious Peritonitis Virus (FIPV) is a highly lethal pathogen affecting cats worldwide. Developing effective antiviral treatments is crucial for managing this disease. This study investigates the potential of flavonoids to act as antiviral agents and allosteric modulators against the FIPV spike protein using molecular docking simulations. Thirteen flavonoids were docked against the FIPV spike protein (PDB ID: 6JX7) in both ligand-free (cleaned) and ligand-bound (uncleaned) states to assess their binding affinities and potential allosteric effects. The docking results revealed that all tested flavonoids exhibited strong binding affinities, with docking scores ranging from -7.9 to -9.6 kcal/mol in the cleaned receptor state. Notably, Hesperidin, Morin, Hesperetin, and Quercetin maintained or even improved their binding affinities in the presence of native ligands, suggesting their potential as allosteric modulators. Comparative analysis of the binding modes in the cleaned and uncleaned receptor states further supports the allosteric modulator potential of Morin, Hesperetin, and Hesperidin. These findings highlight the promising role of flavonoids as antiviral agents and allosteric modulators targeting the FIPV spike protein. Further experimental validation and optimization of these compounds could lead to the development of effective treatments for feline infectious peritonitis. This study provides valuable insights into the application of flavonoids in the management of viral diseases and contributes to the ongoing efforts in antiviral drug discovery.

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“…Teriflunomide, a dihydrowhey acid dehydrogenase inhibitor, is an FDA-approved immunomodulator with low cytotoxicity, and used to treat relapse-remission multiple sclerosis in the clinic ( Wiese et al., 2013 ; Scott, 2019 ; Barua et al., 2023 ; Lang et al., 2023 ). Up to now, no study on the antifungal activity of teriflunomide has so far been reported.…”

Section: Introductionmentioning

confidence: 99%

Synergistic potential of teriflunomide with fluconazole against resistant Candida albicans in vitro and in vivo

Li,

Kong,

Sun

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionCandida albicans is the primary cause of systemic candidiasis, which is involved in high morbidity and mortality. Drug resistance exacerbates these problems. In addition, there are limited antifungal drugs available. In order to solve these problems, combination therapy has aroused great interest. Teriflunomide is an immunosuppressant. In the present work, we aimed to identify whether teriflunomide can reverse the resistance of Candida albicans in the presence of sub-inhibitory concentrations of fluconazole in vitro and in vivo.MethodsSeven Candida albicans isolates were used in this study. Susceptibility of Candida albicans in vitro to the drugs was determined using a checkerboard microdilution assay in accordance with the recommendations of the Clinical and Laboratory Standards Institute. The effects of drugs on biofilm biomass of Candida albicans were determined by crystal violet staining. The development ability of Candida albicans hyphae was performed using a modified broth microdilution method. Galleria mellonella was used for testing the in vivo efficacy of the combination therapies. ResultsWe found that the combination of teriflunomide (64 µg/mL) and fluconazole (0.5-1 µg/mL) has a significant synergistic effect in all resistant Candida albicans isolates (n=4). Also, this drug combination could inhibit the immature biofilm biomass and hyphae formation of resistant Candida albicans. Galleria mellonella was used for testing the in vivo efficacy of this combination therapies. As for the Galleria mellonella larvae infected by resistant Candida albicans, teriflunomide (1.6 µg/larvae) combined with fluconazole (1.6 µg/larvae) significantly increased their survival rates, and reduced the fungal burden, as well as damage of tissue in comparison to that in the control group or drug monotherapy group. ConclusionThese results expand our knowledge about the antifungal potential of teriflunomide as an adjuvant of existing antifungal drugs, and also open new perspectives in the treatment of resistant Candida albicans based on repurposing clinically available nonantifungal drugs.

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Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus

Cited by 4 publications

References 46 publications

Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses

Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses

Theoretical studies of phytochemicals with feline infectious peritonitis virus proteins: a search for novel antivirals

Synergistic potential of teriflunomide with fluconazole against resistant Candida albicans in vitro and in vivo

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