Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Line
2.2. Antiviral Drugs
2.3. FIPV and Quantification of FIPV via qRT-PCR
2.4. The 50% Tissue Culture Infective Dose (TCID50) of FIPV Stock
2.5. Cytotoxicity of the Antiviral Drugs
2.6. Cell Viability Assay of the Antiviral Drugs
2.7. Antiviral Efficacies of the Drugs
2.8. Statistical Analysis
3. Results
3.1. Effect of Initial Inocula and Incubation Times on Anti-FIPV Efficacy of GS441524
3.2. Effect of Different Addition and Removal Times of GS441524 on the Anti-FIPV Efficacy
3.3. Cytotoxicity and Cell Viability of Antiviral Drugs
3.4. Antiviral Efficacies of Six Antiviral Drugs
3.5. Selectivity Index (SI) of Six Drugs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug Name | Drug Category | Viral Target | Investigated CoVs * | References |
---|---|---|---|---|
GS441524 | Adenosine nucleotide analog | Inhibition of RNA systhesis | FIPV, SARS-CoV-2, MERS-CoV | [5,6,9,13,14] |
Nirmatrelvir | 3C-like Protease inhibitor | Inhibition of RNA systhesis | FIPV, SARS-CoV-2 | [15] |
Molnupiravir | Isopropyl ester cytidine analog | Inhibition of RNA systhesis | FIPV, SARS-CoV-2, MERS-CoV | [8,16,17] |
Ruxolitinib | Kinase inhibitor | Inhibition of viral entry | SARS-CoV-2 | [18] |
Ritonavir | Antiretroviral protease inhibitor | Cleavage of viral polyproteins | FIPV, SARS-CoV-2 | [19,20] |
Teriflunomide | Dihydroorotate dehydrogenase inhibitor | Inhibition of RNA systhesis | SARS-CoV-2 | [21] |
FIPV Inoculum | 48 h | 72 h | ||||
---|---|---|---|---|---|---|
No Drug | GS441524 | Fold Reduced | No Drug | GS441524 | Fold Reduced | |
2.50 × 104 * | 5.91 × 106 | 2.76 × 103 | 2.14 × 103 | 4.67 × 106 | 3.24 × 103 | 1.44 × 103 |
2.50 × 103 | 1.17 × 107 | 3.48 × 102 | 3.36 × 104 | 5.18 × 106 | 2.09 × 102 | 2.47 × 104 |
2.50 × 102 | 1.23 × 107 | 4.60 × 101 | 2.67 × 105 | 9.05 × 106 | 2.36 × 101 | 3.83 × 105 |
Treatments * | Increase in Viral Load | |||||
---|---|---|---|---|---|---|
24 h | Fold Increase ** | 48 h | Fold Increase | 72 h | Fold Increase | |
−2 hpi *** | 1.97 × 104 | 0.79 | 2.94 × 105 | 11 | 6.89 × 106 | 275 |
−2 & +1 hpi | 2.47 × 104 | 0.99 | 1.03 × 104 | 0.41 | 1.62 × 104 | 0.65 |
0 hpi | 2.58 × 104 | 1.03 | 1.97 × 104 | 0.79 | 2.04 × 104 | 0.82 |
+1 hpi | 2.84 × 104 | 1.14 | 1.52 × 104 | 0.61 | 1.39 × 104 | 0.56 |
No drug | 1.63 × 106 | 65 | 5.82 × 106 | 232 | 5.48 × 106 | 219 |
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Barua, S.; Kaltenboeck, B.; Juan, Y.-C.; Bird, R.C.; Wang, C. Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus. Vet. Sci. 2023, 10, 513. https://doi.org/10.3390/vetsci10080513
Barua S, Kaltenboeck B, Juan Y-C, Bird RC, Wang C. Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus. Veterinary Sciences. 2023; 10(8):513. https://doi.org/10.3390/vetsci10080513
Chicago/Turabian StyleBarua, Subarna, Bernhard Kaltenboeck, Yen-Chen Juan, Richard Curtis Bird, and Chengming Wang. 2023. "Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus" Veterinary Sciences 10, no. 8: 513. https://doi.org/10.3390/vetsci10080513