Protease inhibitors broadly effective against feline, ferret and mink coronaviruses
| Autor: | William C. Groutas, Kyeong-Ok Chang, Amanda Honeyfield, A.D. Rathnayake, Anushka C. Galasiti Kankanamalage, Yunjeong Kim, Krishani Dinali Perera |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.drug_class medicine.medical_treatment viruses Virulence medicine.disease_cause Antiviral Agents Article 03 medical and health sciences Structure-Activity Relationship Viral Proteins Virology biology.animal medicine Fluorescence Resonance Energy Transfer Animals Protease inhibitor (pharmacology) Protease Inhibitors Mink Coronavirus Pharmacology CATS Protease biology 3C Viral Proteases Ferrets virus diseases Feline infectious peritonitis 3. Good health Molecular Docking Simulation Cysteine Endopeptidases 030104 developmental biology Cats Antiviral drug |
| Zdroj: | Antiviral Research |
| ISSN: | 1872-9096 |
| Popis: | Ferret and mink coronaviruses typically cause catarrhal diarrhea in ferrets and minks, respectively. In recent years, however, systemic fatal coronavirus infection has emerged in ferrets, which resembles feline infectious peritonitis (FIP) in cats. FIP is a highly fatal systemic disease caused by a virulent feline coronavirus infection in cats. Despite the importance of coronavirus infections in these animals, there are no effective commercial vaccines or antiviral drugs available for these infections. We have previously reported the efficacy of a protease inhibitor in cats with FIP, demonstrating that a virally encoded 3C-like protease (3CLpro) is a valid target for antiviral drug development for coronavirus infections. In this study, we extended our previous work on coronavirus inhibitors and investigated the structure-activity relationships of a focused library of protease inhibitors for ferret and mink 3CLpro. Using the fluorescence resonance energy transfer assay, we identified potent inhibitors broadly effective against feline, ferret and mink coronavirus 3CLpro. Multiple amino acid sequence analysis and modelling of 3CLpro of ferret and mink coronaviruses were conducted to probe the structural basis for these findings. The results of this study provide support for further research to develop broad-spectrum antiviral agents for multiple coronavirus infections. To the best of our knowledge, this is the first report on small molecule inhibitors of ferret and mink coronaviruses. |
| Databáze: | OpenAIRE |
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